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Journal articles on the topic 'PBPK simulator'

Author: Grafiati

Published: 5 June 2025

Last updated: 15 July 2025

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1

Cvijić, Sandra, Jelisaveta Ignjatović, Jelena Parojčić, and Svetlana Ibrić. "The emerging role of physiologically-based pharmacokinetic/biopharmaceutics modeling in formulation development." Arhiv za farmaciju 71, no. 4 (2021): 318–35. http://dx.doi.org/10.5937/arhfarm71-32479.

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Computer-based (in silico) modeling & simulation tools have been embraced in different fields of pharmaceutics for a variety of applications. Among these, physiologically-based pharmacokinetic/biopharmaceutics modeling (PBPK/PBBM) emerged as a particularly useful tool in formulation development. PBPK/PBBM facilitated strategies have been increasingly evaluated over the past few years, as demonstrated by several reports from the pharmaceutical industry, and a number of research and review papers on this subject. Also, the leading regulatory authorities have recently issued guidance on the u

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Yoon, Deok Yong, SeungHwan Lee, In-Jin Jang, et al. "Prediction of Drug–Drug Interaction Potential of Tegoprazan Using Physiologically Based Pharmacokinetic Modeling and Simulation." Pharmaceutics 13, no. 9 (2021): 1489. http://dx.doi.org/10.3390/pharmaceutics13091489.

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This study aimed to develop a physiologically based pharmacokinetic (PBPK) model of tegoprazan and to predict the drug–drug interaction (DDI) potential between tegoprazan and cytochrome P450 (CYP) 3A4 perpetrators. The PBPK model of tegoprazan was developed using SimCYP Simulator® and verified by comparing the model-predicted pharmacokinetics (PKs) of tegoprazan with the observed data from phase 1 clinical studies, including DDI studies. DDIs between tegoprazan and three CYP3A4 perpetrators were predicted by simulating the difference in tegoprazan exposure with and without perpetrators, after

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Kalsoom, Samia, Muhammad Fawad Rasool, Imran Imran, Hamid Saeed, Tanveer Ahmad, and Faleh Alqahtani. "A Comprehensive Physiologically Based Pharmacokinetic Model of Nadolol in Adults with Renal Disease and Pediatrics with Supraventricular Tachycardia." Pharmaceuticals 17, no. 2 (2024): 265. http://dx.doi.org/10.3390/ph17020265.

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Nadolol is a long-acting non-selective β–adrenergic antagonist that helps treat angina and hypertension. The current study aimed to develop and validate the physiologically based pharmacokinetic model (PBPK) of nadolol in healthy adults, renal-compromised, and pediatric populations. A comprehensive PBPK model was established by utilizing a PK-Sim simulator. After establishing and validating the model in healthy adults, pathophysiological changes i.e., blood flow, hematocrit, and GFR that occur in renal failure were incorporated in the developed model, and the drug exposure was assessed through

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Pei, Ling, Run Li, Hong Zhou, et al. "A Physiologically Based Pharmacokinetic Approach to Recommend an Individual Dose of Tacrolimus in Adult Heart Transplant Recipients." Pharmaceutics 15, no. 11 (2023): 2580. http://dx.doi.org/10.3390/pharmaceutics15112580.

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Tacrolimus is the principal immunosuppressive drug which is administered after heart transplantation. Managing tacrolimus therapy is challenging due to a narrow therapeutic index and wide pharmacokinetic (PK) variability. We aimed to establish a physiologically based pharmacokinetic (PBPK) model of tacrolimus in adult heart transplant recipients to optimize dose regimens in clinical practice. A 15-compartment full-PBPK model (Simbiology® Simulator, version 5.8.2) was developed using clinical observations from 115 heart transplant recipients. This study detected 20 genotypes associated with tac

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Rasool, Muhammad F., Sundus Khalid, Abdul Majeed, et al. "Development and Evaluation of Physiologically Based Pharmacokinetic Drug–Disease Models for Predicting Rifampicin Exposure in Tuberculosis and Cirrhosis Populations." Pharmaceutics 11, no. 11 (2019): 578. http://dx.doi.org/10.3390/pharmaceutics11110578.

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The physiologically based pharmacokinetic (PBPK) approach facilitates the construction of novel drug–disease models by allowing incorporation of relevant pathophysiological changes. The aim of the present work was to explore and identify the differences in rifampicin pharmacokinetics (PK) after the application of its single dose in healthy and diseased populations by using PBPK drug–disease models. The Simcyp® simulator was used as a platform for modeling and simulation. The model development process was initiated by predicting rifampicin PK in healthy population after intravenous (i.v) and or

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Jeong, Hyeon-Cheol, Min-Gul Kim, Zhuodu Wei, et al. "Integration of a Physiologically Based Pharmacokinetic and Pharmacodynamic Model for Tegoprazan and Its Metabolite: Application for Predicting Food Effect and Intragastric pH Alterations." Pharmaceutics 14, no. 6 (2022): 1298. http://dx.doi.org/10.3390/pharmaceutics14061298.

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A physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model for tegoprazan and its major metabolite M1 was developed to predict PK and PD profiles under various scenarios. The PBPK model for tegoprazan and M1 was developed and predicted using the SimCYP® simulator and verified using clinical study data obtained after a single administration of tegoprazan. The established PBPK/PD model was used to predict PK profiles after repeated administrations of tegoprazan, postprandial PK profiles, and intragastric pH changes. The predicted tegoprazan and M1 concentration–time profiles fit the

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Alqahtani, Faleh, Abdullah H. Alruwaili, Mohammed S. Alasmari, et al. "A Physiologically Based Pharmacokinetic Model to Predict Systemic Ondansetron Concentration in Liver Cirrhosis Patients." Pharmaceuticals 16, no. 12 (2023): 1693. http://dx.doi.org/10.3390/ph16121693.

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Introduction: Ondansetron is a drug that is routinely prescribed for the management of nausea and vomiting associated with cancer, radiation therapy, and surgical operations. It is mainly metabolized in the liver, and it might accumulate in patients with hepatic impairment and lead to unwanted adverse events. Methods: A physiologically based pharmacokinetic (PBPK) model was developed to predict the exposure of ondansetron in healthy and liver cirrhosis populations. The population-based PBPK simulator PK-Sim was utilized for simulating ondansetron exposure in healthy and liver cirrhosis populat

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van Hove, Hedwig, Vera Bukkems, Damian Roelofsen, et al. "3 The exposure to and efficacy of doravirine in pregnant women as assessed by physiologically-based pharmacokinetic modelling." Archives of Disease in Childhood 108, no. 6 (2023): A1.3—A1. http://dx.doi.org/10.1136/archdischild-2023-esdppp.3.

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IntroductionDoravirine is currently not recommended for pregnant women living with HIV due to the lack of efficacy and safety data. Physiological changes during pregnancy can significantly decrease drug exposure, and, thereby, lower the efficacy. Awaiting clinical data, this study aimed to predict maternal and fetal doravirine exposure by integrating human placenta perfusion experiments with pregnancy physiologically-based pharmacokinetic (PBPK) modelling.MethodsAn existing and validated three-compartment PBPK model of doravirine for a healthy, non-pregnant population was modified to a 18-comp

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Witkowski, Jakub, Sebastian Polak, Dariusz Pawelec, and Zbigniew Rogulski. "In Vitro/In Vivo Translation of Synergistic Combination of MDM2 and MEK Inhibitors in Melanoma Using PBPK/PD Modelling: Part III." International Journal of Molecular Sciences 24, no. 3 (2023): 2239. http://dx.doi.org/10.3390/ijms24032239.

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The development of in vitro/in vivo translational methods and a clinical trial framework for synergistically acting drug combinations are needed to identify optimal therapeutic conditions with the most effective therapeutic strategies. We performed physiologically based pharmacokinetic–pharmacodynamic (PBPK/PD) modelling and virtual clinical trial simulations for siremadlin, trametinib, and their combination in a virtual representation of melanoma patients. In this study, we built PBPK/PD models based on data from in vitro absorption, distribution, metabolism, and excretion (ADME), and in vivo

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Reig-López, Javier, María del Mar Maldonado, Matilde Merino-Sanjuan, et al. "Physiologically-Based Pharmacokinetic/Pharmacodynamic Model of MBQ-167 to Predict Tumor Growth Inhibition in Mice." Pharmaceutics 12, no. 10 (2020): 975. http://dx.doi.org/10.3390/pharmaceutics12100975.

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MBQ-167 is a dual inhibitor of the Rho GTPases Rac and Cdc42 that has shown promising results as an anti-cancer therapeutic at the preclinical stage. This drug has been tested in vitro and in vivo in metastatic breast cancer mouse models. The aim of this study is to develop a physiologically based pharmacokinetic/pharmacodynamic (PBPK-PD) model of MBQ-167 to predict tumor growth inhibition following intraperitoneal (IP) administration in mice bearing Triple Negative and HER2+ mammary tumors. PBPK and Simeoni tumor growth inhibition (TGI) models were developed using the Simcyp V19 Animal Simula

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Arora, Priyanka, Gary Gudelsky, and Pankaj B. Desai. "Gender-based differences in brain and plasma pharmacokinetics of letrozole in sprague-dawley rats: Application of physiologically-based pharmacokinetic modeling to gain quantitative insights." PLOS ONE 16, no. 4 (2021): e0248579. http://dx.doi.org/10.1371/journal.pone.0248579.

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Based on the discovery that the estrogen synthase aromatase (CYP19A1) is abundantly expressed in high- grade gliomas, the aromatase inhibitor, letrozole is being investigated in pre-clinical models as a novel agent against this malignancy. Here, we investigated the systemic and brain pharmacokinetics of letrozole following single and steady state dosing in both male and female Sprague-Dawley rats. Furthermore, we employed physiologically-based pharmacokinetic (PBPK) modeling to gain quantitative insights into the blood-brain barrier penetration of this drug. Letrozole (4 mg/kg) was administere

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Berezowska, Monika, Paola Coppola, Venkatesh Pilla Reddy, and Pradeep Sharma. "Physiologically Based Pharmacokinetic Modelling of UGT Substrate Drugs Lamotrigine and Raltegravir during Pregnancy." Future Pharmacology 4, no. 2 (2024): 317–35. http://dx.doi.org/10.3390/futurepharmacol4020018.

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Pregnancy is associated with various physiological changes that can significantly impact the disposition of drugs. To further the insight into how pregnancy affects the pharmacokinetics of drugs at different stages, clinical studies can be simulated using Physiologically Based Pharmacokinetic modelling. PBPK modelling of drugs metabolised by Phase I enzymes (CYPs) in pregnant population models had been reported in the past, while its use in Phase II (UGTs) is not known. In this study, based on the results of a recent meta-analysis, lamotrigine (UGT1A4) and raltegravir (UGT1A1) were selected as

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Khalid, Sundus, Muhammad Fawad Rasool, Imran Imran, et al. "A Physiologically Based Pharmacokinetic Model for Predicting Diazepam Pharmacokinetics after Intravenous, Oral, Intranasal, and Rectal Applications." Pharmaceutics 13, no. 9 (2021): 1480. http://dx.doi.org/10.3390/pharmaceutics13091480.

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Diazepam is one of the most prescribed anxiolytic and anticonvulsant that is administered through intravenous (IV), oral, intramuscular, intranasal, and rectal routes. To facilitate the clinical use of diazepam, there is a need to develop formulations that are convenient to administer in ambulatory settings. The present study aimed to develop and evaluate a physiologically based pharmacokinetic (PBPK) model for diazepam that is capable of predicting its pharmacokinetics (PK) after IV, oral, intranasal, and rectal applications using a whole-body population-based PBPK simulator, Simcyp®. The mod

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Witkowski, Jakub, Sebastian Polak, Zbigniew Rogulski, and Dariusz Pawelec. "In Vitro/In Vivo Translation of Synergistic Combination of MDM2 and MEK Inhibitors in Melanoma Using PBPK/PD Modelling: Part II." International Journal of Molecular Sciences 23, no. 19 (2022): 11939. http://dx.doi.org/10.3390/ijms231911939.

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The development of in vitro/in vivo translational methods for synergistically acting drug combinations is needed to identify the most effective therapeutic strategies. We performed PBPK/PD modelling for siremadlin, trametinib, and their combination at various dose levels and dosing schedules in an A375 xenografted mouse model (melanoma cells). In this study, we built models based on in vitro ADME and in vivo PK/PD data determined from the literature or estimated by the Simcyp Animal simulator (V21). The developed PBPK/PD models allowed us to account for the interactions between siremadlin and

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Avvari, Suvarchala Kiranmai, Jaclyn A. Cusumano, Vamshi Krishna Jogiraju, Pooja Manchandani, and David R. Taft. "PBPK Modeling of Azithromycin Systemic Exposure in a Roux-en-Y Gastric Bypass Surgery Patient Population." Pharmaceutics 15, no. 11 (2023): 2520. http://dx.doi.org/10.3390/pharmaceutics15112520.

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In this investigation, PBPK modeling using the Simcyp® Simulator was performed to evaluate whether Roux-en-Y gastric bypass (RYGB) surgery impacts the oral absorption and bioavailability of azithromycin. An RYGB surgery patient population was adapted from the published literature and verified using the same probe medications, atorvastatin and midazolam. Next, a PBPK model of azithromycin was constructed to simulate changes in systemic drug exposure after the administration of different oral formulations (tablet, suspension) to patients pre- and post-RYGB surgery using the developed and verifie

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Chang, Ming, Sai Bathena, Lisa J. Christopher, Hong Shen, and Amit Roy. "Prediction of drug–drug interaction potential mediated by transporters between dasatinib and metformin, pravastatin, and rosuvastatin using physiologically based pharmacokinetic modeling." Cancer Chemotherapy and Pharmacology 89, no. 3 (2022): 383–92. http://dx.doi.org/10.1007/s00280-021-04394-z.

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Abstract Purpose Recent in vitro studies demonstrated that dasatinib inhibits organic cation transporter 2 (OCT2), multidrug and toxin extrusion proteins (MATEs), and organic anion transporting polypeptide 1B1/1B3 (OATP1B1/1B3). We developed a physiologically based pharmacokinetic (PBPK) model to assess drug–drug interaction (DDI) potential between dasatinib and known substrates for these transporters in a virtual population. Methods The dasatinib PBPK model was constructed using Simcyp® Simulator by combining its physicochemical properties, in vitro data, in silico predictions, and pharmacoki

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Shuklinova, Olha, Gabriela Wyszogrodzka-Gaweł, Ewelina Baran, et al. "Can 3D Printed Tablets Be Bioequivalent and How to Test It: A PBPK Model Based Virtual Bioequivalence Study for Ropinirole Modified Release Tablets." Pharmaceutics 16, no. 2 (2024): 259. http://dx.doi.org/10.3390/pharmaceutics16020259.

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As the field of personalized dosing develops, the pharmaceutical manufacturing industry needs to offer flexibility in terms of tailoring the drug release and strength to the individual patient’s needs. One of the promising tools which have such capacity is 3D printing technology. However, manufacturing small batches of drugs for each patient might lead to huge test burden, including the need to conduct bioequivalence trials of formulations to support the change of equipment or strength. In this paper we demonstrate how to use 3D printing in conjunction with virtual bioequivalence trials based

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Karkhanis, Aneesh V., Matthew D. Harwood, Felix Stader, Frederic Y. Bois та Sibylle Neuhoff. "Applications of the Cholesterol Metabolite, 4β-Hydroxycholesterol, as a Sensitive Endogenous Biomarker for Hepatic CYP3A Activity Evaluated within a PBPK Framework". Pharmaceutics 16, № 10 (2024): 1284. http://dx.doi.org/10.3390/pharmaceutics16101284.

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Background/Objectives: Plasma levels of 4β-hydroxycholesterol (4β-OHC), a CYP3A-specific metabolite of cholesterol, are elevated after administration of CYP3A inducers like rifampicin and carbamazepine. To simulate such plasma 4β-OHC increase, we developed a physiologically based pharmacokinetic (PBPK) model of cholesterol and 4β-OHC in the Simcyp PBPK Simulator (Version 23, Certara UK Ltd.) using a middle-out approach. Methods: Relevant physicochemical properties and metabolic pathway data for CYP3A and CYP27A1 was incorporated in the model. Results: The PBPK model recovered the observed base

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Krumpholz, Laura, Sebastian Polak, and Barbara Wiśniowska. "IVPT Data Heterogeneity – How to Make Sense out of It Using PBPK Model." Acta Poloniae Pharmaceutica - Drug Research 81, no. 6 (2025): 959–71. https://doi.org/10.32383/appdr/200889.

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Physiologically based pharmacokinetic (PBPK) modeling is gaining importance in drug development. Recently, the Multi-phase Multi-layer Mechanistic Dermal Absorption (MPML MechDermA) model for simulating topical application was published and subsequently repurposed for simulating in vitro permeation tests using pig ear skin. In previous studies, the model validation process was conducted with caffeine. The current work describes literature experimental data–based development and verification of PBPK model of testosterone permeation through human and pig ear skin under in vitro conditions using

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Pansari, A., K. Abduljalil, and T. Johnson. "O07 Predictive performance of a physiologically based pharmacokinetic model of caffeine in the preterm population." Archives of Disease in Childhood 104, no. 6 (2019): e3.2-e3. http://dx.doi.org/10.1136/archdischild-2019-esdppp.7.

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BackgroundCaffeine has been extensively used in the treatment of apnoea in premature infants,1 its disposition varies with postnatal age2 and can differ markedly between premature and term neonates.MethodsThe Preterm population within the Simcyp Simulator V18R1 population library was used to replicate clinical studies to predict caffeine exposure after single3 and multiple4 intravenous administration to preterm neonates of gestational weeks 28.5 and 29 (28–33) respectively, ranging in postnatal age of 3–30 days and 0–3 days respectively. Predictive performance of the Physiologically Based Phar

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Rasool, Muhammad, Feras Khalil, and Stephanie Läer. "PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELS FOR ADULT AND PAEDIATRIC CHRONIC HEART FAILURE PATIENTS USING THE EXAMPLE OF CARVEDILOL TREATED PATIENTS." Archives of Disease in Childhood 101, no. 1 (2015): e1.45-e1. http://dx.doi.org/10.1136/archdischild-2015-310148.5.

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BackgroundIn chronic heart failure (CHF), the changes in organ blood flows can significantly affect the metabolism of drugs with high hepatic extraction. Physiologically based pharmacokinetic modelling (PBPK) can be utilized to predict clearances of high extraction drugs like carvedilol in CHF. The adult PBPK-CHF model after its evaluation in adults, can be scaled to pediatrics using population based PBPK simulator.MethodsAfter a literature search for model input parameters, two-PBPK models were developed which differed only on the basis of clearance as, model-1 was based on human liver and in

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Architha, Aithal, Aithal Shubhrajyotsna, and S. Aithal P. "Case Study on Certara's Simcyp PBPK Simulator to Eliminate Lengthy Clinical Trails." International Journal of Health Sciences and Pharmacy (IJHSP) 6, no. 2 (2022): 69–109. https://doi.org/10.5281/zenodo.7186370.

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<strong>Background/Purpose:</strong> <em>Analysis and new interpretation of the existing information are equivalent to creating new knowledge. A case study is an example of exploratory research and allows researchers to analyze the available information using a systematic analysis framework. In this paper, a case study on a clinical research simulation software product called Simcyp is offered by a global company Certara to its clients in the pharmaceutical industry. </em> <strong>Objective:</strong> <em>To know the current status of model-based drug development simulation software, with speci

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Architha, Aithal, Aithal Shubhrajyotsna, and S. Aithal P. "Case Study on Certara's Simcyp PBPK Simulator to Eliminate Lengthy Clinical Trials." International Journal of Health Sciences and Pharmacy (IJHSP) 6, no. 2 (2022): 69–109. https://doi.org/10.5281/zenodo.7223403.

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<strong>Background/Purpose:</strong> <em>Analysis and new interpretation of the existing information are equivalent to creating new knowledge. A case study is an example of exploratory research and allows researchers to analyze the available information using a systematic analysis framework. In this paper, a case study on a clinical research simulation software product called Simcyp is offered by a global company Certara to its clients in the pharmaceutical industry. </em> <strong>Objective:</strong> <em>To know the current status of model-based drug development simulation software, with speci

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Shah, Harsh, Kushal Shah, Bhavin Gajera, Rutesh H. Dave, and David R. Taft. "Developing a Formulation Strategy Coupled with PBPK Modeling and Simulation for the Weakly Basic Drug Albendazole." Pharmaceutics 15, no. 4 (2023): 1040. http://dx.doi.org/10.3390/pharmaceutics15041040.

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Albendazole (ABZ) is a weakly basic drug that undergoes extensive presystemic metabolism after oral administration and converts to its active form albendazole sulfoxide (ABZ_SO). The absorption of albendazole is limited by poor aqueous solubility, and dissolution is the rate-limiting step in the overall exposure of ABZ_SO. In this study, PBPK modeling was used to identify formulation-specific parameters that impact the oral bioavailability of ABZ_SO. In vitro experiments were carried out to determine pH solubility, precipitation kinetics, particle size distribution, and biorelevant solubility.

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Templeton, Ian E., Terry Podoll, Cecile Marie Krejsa, and J. Greg Slatter. "A Mechanistic Physiologically Based Pharmacokinetic (PBPK) Drug Interaction Model for the Mouse Double Minute 2 (MDM2) Inhibitor KRT-232." Blood 136, Supplement 1 (2020): 9–10. http://dx.doi.org/10.1182/blood-2020-135987.

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Background: KRT-232 is a potent, selective, orally available, targeted inhibitor of human MDM2 homolog interactions with tumor suppressor protein 53 (p53). KRT-232 is under development for treatment of myeloproliferative neoplasms, acute myeloid leukemia and Merkel cell carcinoma. KRT-232 is a highly permeable 568.6 g/mol, monoprotic carboxylic acid (pKa 4.35); elimination involves primarily biliary-fecal excretion of an acyl glucuronide metabolite (M1) and enteric glucuronide hydrolysis with enterohepatic recirculation of parent drug. M1 is a 744.7 g/mol monoprotic acid with pKa 3.32 and 1/5t

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Chirumamilla, Siri Kalyan, Venkatesh Teja Banala, Masoud Jamei, and David B. Turner. "Mechanistic PBPK Modelling to Predict the Advantage of the Salt Form of a Drug When Dosed with Acid Reducing Agents." Pharmaceutics 13, no. 8 (2021): 1169. http://dx.doi.org/10.3390/pharmaceutics13081169.

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Acid reducing agents (ARAs) reduce the dissolution rate of weakly basic drugs in the stomach potentially leading to lower bioavailability. Formulating the API as a rapidly dissolving salt is one strategy employed to reduce the impact of ARAs on dissolution of such drugs. In the present work, a model drug was selected with an immediate release formulation of the free base dosed in both the absence and presence of the ARA famotidine. In the latter case, bioavailability is restricted and several salt formulations were investigated. To simulate these drug products a mechanistic physiologically bas

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O’Dwyer, Patrick J., Georgios Imanidis, Karl J. Box, and Christos Reppas. "On the Usefulness of Two Small-Scale In Vitro Setups in the Evaluation of Luminal Precipitation of Lipophilic Weak Bases in Early Formulation Development." Pharmaceutics 12, no. 3 (2020): 272. http://dx.doi.org/10.3390/pharmaceutics12030272.

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A small-scale biphasic dissolution setup and a small-scale dissolution-permeation (D-P) setup were evaluated for their usefulness in simulating the luminal precipitation of three lipophilic weak bases—dipyridamole, ketoconazole and itraconazole. The transition from the gastric to intestinal environment was incorporated into both experimental procedures. Emulsification during the biphasic dissolution experiments had a minimal impact on the data, when appropriate risk mitigation steps were incorporated. Precipitation parameters estimated from the in vitro data were inputted into the Simcyp® phys

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Hafsa, Hafsa, Ammara Zamir, Muhammad Fawad Rasool, et al. "Development and Evaluation of a Physiologically Based Pharmacokinetic Model of Labetalol in Healthy and Diseased Populations." Pharmaceutics 14, no. 11 (2022): 2362. http://dx.doi.org/10.3390/pharmaceutics14112362.

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Labetalol is a drug that exhibits both alpha and beta-adrenergic receptor-blocking properties. The American Heart Association/American Stroke Association (AHA/ASA) has recommended labetalol as an initial treatment option for the management of severe hypertension. The physiologically based pharmacokinetic (PBPK) model is an in silico approach to determining the pharmacokinetics (PK) of a drug by incorporating blood flow and tissue composition of the organs. This study was conducted to evaluate the primary reasons for the difference in PK after intravenous (IV) and oral administration in healthy

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Shah, Kushal, Briann Fischetti, Agnes Cha, and David R. Taft. "Using PBPK Modeling to Predict Drug Exposure and Support Dosage Adjustments in Patients With Renal Impairment: An Example with Lamivudine." Current Drug Discovery Technologies 17, no. 3 (2020): 387–96. http://dx.doi.org/10.2174/1570163816666190214164916.

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Background: Lamivudine is a nucleoside reverse transcriptase inhibitor used to treat HIV and hepatitis B. It is primarily cleared by the kidney with renal secretion mediated by OCT2 and MATE. Objective: To use PBPK modeling to assess the impact of renal impairment on lamivudine pharmacokinetics using the Simcyp® Simulator. Methods: The model incorporated the Simcyp® Mechanistic Kidney Model option to predict renal disposition. The model was initially verified using the Simcyp® Healthy Volunteer population. Two discrete patient populations were then created for moderate (GFR 10-40 mL/min) and s

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Chen, Lu, Ning Ji, Min Zhang, and Wanyi Chen. "The Influence of Wuzhi Capsule on the Pharmacokinetics of Cyclophosphamide." Recent Patents on Anti-Cancer Drug Discovery 17, no. 2 (2022): 195–203. http://dx.doi.org/10.2174/1574892816666211110152119.

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Background: Cyclophosphamide is approved for the treatment of a variety of tumors, yet the use of cyclophosphamide is limited by kidney and liver toxicity. In the clinic, the Wuzhi capsule is approved to attenuate cyclophosphamide toxicity in the kidney and liver. Objective: We aimed to investigate the effects of the principal ingredients of Wuzhi capsule, schisandrin A (SIA) and schisantherin A (STA), on the pharmacokinetics of cyclophosphamide. Methods: The essential pharmacokinetic data and physicochemical parameters of SIA, STA, and cyclophosphamide were collected. Physiologically based ph

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Abduljalil, K., TN Johnson, and M. Jamei. "P01 Application of feto-placental-maternal physiologically-based pharmacokinetic model to predict tenofovir concentration during pregnancy." Archives of Disease in Childhood 104, no. 6 (2019): e17.2-e18. http://dx.doi.org/10.1136/archdischild-2019-esdppp.40.

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BackgroundTenofovir is a drug used in combination with other anti-HIV drugs to treat patients with HIV-1 infection. It is used during pregnancy to reduce the risk of HIV transmission to the child. The aim of this work is to use a Physiologically-Based Pharmacokinetic (PBPK) model for prediction of maternal and fetal tenofovir concentration at birth.MethodsA full Feto-Placental-Maternal PBPK model that includes placenta as a 3-comparment permeability limited organ and 14 compartments for different fetal organs was developed using physiological1,2 and drug specific parameters3 to predict tenofov

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Sychterz, Caroline, Iain Gardner, Manting Chiang, et al. "Performance Verification of CYP2C19 Enzyme Abundance Polymorphism Settings within the Simcyp Simulator v21." Metabolites 12, no. 10 (2022): 1001. http://dx.doi.org/10.3390/metabo12101001.

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Physiologically based pharmacokinetic (PBPK) modeling has a number of applications, including assessing drug–drug interactions (DDIs) in polymorphic populations, and should be iteratively refined as science progresses. The Simcyp Simulator is annually updated and version 21 included updates to hepatic and intestinal CYP2C19 enzyme abundance, including addition of intermediate and rapid metabolizer phenotypes and changes to the ultra-rapid metabolizer enzyme abundance, with implications for population clearance and DDI predictions. This work details verification of the updates with sensitive CY

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Johnson, Trevor, Fiskani Kondowe, and Iain Gardner. "21 Physiologically based pharmacokinetic model to simulate midazolam pharmacokinetics in a paediatric US population." Archives of Disease in Childhood 108, no. 6 (2023): A7.2—A7. http://dx.doi.org/10.1136/archdischild-2023-esdppp.21.

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There has been a lot of academic and regulatory interest regarding bridging clinical trials between different populations. The aims of this study were to:Develop a PBPK model for the US paediatric population (USPP) incorporating demographic and CYP3A5 phenotype frequency of different ethnic groups (White, Hispanic, Black and Asian).Apply the USPP to predict midazolam pharmacokinetics (PK) of a clinical study performed in the US.Demographic information, height for age and weight for height relationships, and CYP3A5 phenotype frequencies were established for each US ethnic group using NHANES and

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Denic, Kristina Zoran, Sibylle Neuhoff, Joel Reid, and Rachel Kudget. "Abstract A140: A physiologically based pharmacokinetic modeling approach for predicting the exposure of irinotecan and its active metabolite (SN-38) in cancer patients." Molecular Cancer Therapeutics 22, no. 12_Supplement (2023): A140. http://dx.doi.org/10.1158/1535-7163.targ-23-a140.

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Abstract Introduction: Irinotecan is an inhibitor of the topoisomerase I enzyme that is essential in DNA transcription, replication, and repair. It is considered a “backbone” regime in colorectal cancer in adults and in pediatric gliomas to which other antineoplastic agents are added to improve the outcome. It is used as well in the treatment of many other types of adult and pediatric cancers. Irinotecan acts as a prodrug of SN-38 which has approximately 100-1000-fold greater cytotoxic activity. The metabolic and pharmacokinetic behavior of irinotecan is very complex and currently not complete

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Salem, Farzaneh, Trevor Johnson, and Amin Rostami-Hodjegan. "MAPPING IN VITRO AND IN VIVO DERIVED CYP2C9 AND CYP2C19 ONTOGENY FUNCTIONS: A CRITICAL COMPARISON BETWEEN VARIOUS ONTOGENY MODELS." Archives of Disease in Childhood 101, no. 1 (2015): e1.38-e1. http://dx.doi.org/10.1136/archdischild-2015-310148.43.

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In vivo derived ontogeny profiles for CYP1A2 and CYP3A4, show improved clearance (CL) predictions within a paediatric physiologically based pharmacokinetic (p-PBPK) model1. The aim of this study is to derive ontogeny functions (OF) for CYP2C9 and CYP2C19 based on age related CL data on ibuprofen and pantoprazole & lansoprazole, respectively.A literature review was undertaken to collect age related CL data for these probes, the values were deconvoluted back to intrinsic CL values (per mg of liver microsomal protein) as described previously. The 'best-fit' algorithm for ratio of paediatric t

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Sugano, Kiyohiko. "Lost in modelling and simulation?" ADMET and DMPK 9, no. 2 (2021): 75–109. http://dx.doi.org/10.5599/admet.923.

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Over the past few decades, physiologically-based pharmacokinetic modelling (PBPK) has been anticipated to be a powerful tool to improve the productivity of drug discovery and development. However, recently, multiple systematic evaluation studies independently suggested that the predictive power of current oral absorption (OA) PBPK models needs significant improvement. There is some disagreement between the industry and regulators about the credibility of OA PBPK modelling. Recently, the editorial board of AMDET&DMPK has announced the policy for the articles related to PBPK modelling (Model

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Bermejo, Marival, Bart Hens, Joseph Dickens, et al. "A Mechanistic Physiologically-Based Biopharmaceutics Modeling (PBBM) Approach to Assess the In Vivo Performance of an Orally Administered Drug Product: From IVIVC to IVIVP." Pharmaceutics 12, no. 1 (2020): 74. http://dx.doi.org/10.3390/pharmaceutics12010074.

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The application of in silico modeling to predict the in vivo outcome of an oral drug product is gaining a lot of interest. Fully relying on these models as a surrogate tool requires continuous optimization and validation. To do so, intraluminal and systemic data are desirable to judge the predicted outcomes. The aim of this study was to predict the systemic concentrations of ibuprofen after oral administration of an 800 mg immediate-release (IR) tablet to healthy subjects in fasted-state conditions. A mechanistic oral absorption model coupled with a two-compartmental pharmacokinetic (PK) model

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Yoo, Sung-Jun, and Kazuhide Ito. "Numerical prediction of tissue dosimetry in respiratory tract using computer simulated person integrated with physiologically based pharmacokinetic–computational fluid dynamics hybrid analysis." Indoor and Built Environment 27, no. 7 (2017): 877–89. http://dx.doi.org/10.1177/1420326x17694475.

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Indoor environmental quality, e.g. air quality and thermal environments, has a potential impact on residents in indoors. Development of a computer simulated person (CSP) for indoor computational fluid dynamics (CFD) simulation can contribute to the improvement of design and prediction method regarding the interaction between indoor air/thermal environmental factors and human responses. In this study, a CSP integrated with a virtual airway was developed and used to estimate inhalation exposure in an indoor environment. The virtual airway is a numerical respiratory tract model for CFD simulation

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Zunino, Chiara, Virginie Gualano, Haiying Zhou, Viera Lukacova, and Maxime Le Merdy. "Prediction of Monoclonal Antibody Pharmacokinetics in Pediatric Populations Using PBPK Modeling and Simulation." Pharmaceutics 17, no. 7 (2025): 884. https://doi.org/10.3390/pharmaceutics17070884.

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Background: Accurately determining pediatric dosing is essential prior to initiating clinical trials or administering medications in routine clinical settings. In children, ethical considerations demand careful evaluation of both safety and effectiveness. Typically, dosing recommendations for therapeutic proteins, such as monoclonal antibodies (mAbs), are derived from adult dosages using body weight as a scaling factor. However, this method overlooks key physiological and biochemical distinctions between pediatric and adult patients. Therefore, this could lead to the underexposure of mAbs, lim

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Li, Xianfu, En Liang, Xiaoxuan Hong, et al. "In Vitro and In Vivo Bioequivalence Study of 3D-Printed Instant-Dissolving Levetiracetam Tablets and Subsequent Personalized Dosing for Chinese Children Based on Physiological Pharmacokinetic Modeling." Pharmaceutics 14, no. 1 (2021): 20. http://dx.doi.org/10.3390/pharmaceutics14010020.

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Recently, the development of Binder Jet 3D printing technology has promoted the research and application of personalized formulations, which are especially useful for children’s medications. Additionally, physiological pharmacokinetic (PBPK) modeling can be used to guide drug development and drug dose selection. Multiple technologies can be used in combination to increase the safety and effectiveness of drug administration. In this study, we performed in vivo pharmacokinetic experiments in dogs with preprepared 3D-printed levetiracetam instant-dissolving tablets (LEV-IDTs). Bioequivalence anal

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Song, Ling, Cheng Cui, Ying Zhou, et al. "Toward Greater Insights on Applications of Modeling and Simulation in Pregnancy." Current Drug Metabolism 21, no. 9 (2020): 722–41. http://dx.doi.org/10.2174/1389200221666200907143941.

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Pregnant women are often excluded from routine clinical trials. Consequently, appropriate dosing regimens for majority of drugs are unknown in this population, which may lead to unexpected safety issue or insufficient efficacy in this un-studied population. Establishing evidence through the conduct of clinical studies in pregnancy is still a challenge. In recent decades, physiologically-based pharmacokinetic (PBPK) modeling has proven to be useful to support dose selection under various clinical scenarios, such as renal and/or liver impairment, drug-drug interactions, and extrapolation from ad

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Kim, Min-Soo, Yoo-Kyung Song, Ji-Soo Choi, et al. "Physiologically Based Pharmacokinetic Modelling to Predict Pharmacokinetics of Enavogliflozin, a Sodium-Dependent Glucose Transporter 2 Inhibitor, in Humans." Pharmaceutics 15, no. 3 (2023): 942. http://dx.doi.org/10.3390/pharmaceutics15030942.

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Enavogliflozin is a sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor approved for clinical use in South Korea. As SGLT2 inhibitors are a treatment option for patients with diabetes, enavogliflozin is expected to be prescribed in various populations. Physiologically based pharmacokinetic (PBPK) modelling can rationally predict the concentration–time profiles under altered physiological conditions. In previous studies, one of the metabolites (M1) appeared to have a metabolic ratio between 0.20 and 0.25. In this study, PBPK models for enavogliflozin and M1 were developed using published

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Hardiansyah, Deni, Wei Guo, Ali Asgar Attarwala, Peter Kletting, Felix M. Mottaghy, and Gerhard Glatting. "Treatment planning in PRRT based on simulated PET data and a PBPK model." Nuklearmedizin 56, no. 01 (2017): 23–30. http://dx.doi.org/10.3413/nukmed-0819-16-04.

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SummaryAim: To investigate the accuracy of treatment planning in peptide-receptor radionuclide therapy (PRRT) based on simulated PET data (using a PET noise model) and a physiologically based pharmacokinetic (PBPK) model. Methods: The parameters of a PBPK model were fitted to the biokinetic data of 15 patients. True mathematical phantoms of patients (MPPs) were the PBPK model with the fitted parameters. PET measurements after bolus injection of 150 MBq 68Ga-DOTATATE were simulated for the true MPPs. PET noise with typical noise levels was added to the data (i.e. c=0.3 [low], 3, 30 and 300 [hig

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Lim, Andrew, Pradeep Sharma, Oleg Stepanov, and Venkatesh Pilla Reddy. "Application of Modelling and Simulation Approaches to Predict Pharmacokinetics of Therapeutic Monoclonal Antibodies in Pediatric Population." Pharmaceutics 15, no. 5 (2023): 1552. http://dx.doi.org/10.3390/pharmaceutics15051552.

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Ethical regulations and limited paediatric participants are key challenges that contribute to a median delay of 6 years in paediatric mAb approval. To overcome these barriers, modelling and simulation methodologies have been adopted to design optimized paediatric clinical studies and reduce patient burden. The classical modelling approach in paediatric pharmacokinetic studies for regulatory submissions is to apply body weight-based or body surface area-based allometric scaling to adult PK parameters derived from a popPK model to inform the paediatric dosing regimen. However, this approach is l

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Puttrevu, Santosh Kumar, Sumit Arora, Sebastian Polak, and Nikunj Kumar Patel. "Physiologically Based Pharmacokinetic Modeling of Transdermal Selegiline and Its Metabolites for the Evaluation of Disposition Differences between Healthy and Special Populations." Pharmaceutics 12, no. 10 (2020): 942. http://dx.doi.org/10.3390/pharmaceutics12100942.

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A physiologically based pharmacokinetic (PBPK) model of selegiline (SEL), and its metabolites, was developed in silico to evaluate the disposition differences between healthy and special populations. SEL is metabolized to methamphetamine (MAP) and desmethyl selegiline (DMS) by several CYP enzymes. CYP2D6 metabolizes the conversion of MAP to amphetamine (AMP), while CYP2B6 and CYP3A4 predominantly mediate the conversion of DMS to AMP. The overall prediction error in simulated PK, using the developed PBPK model, was within 0.5–1.5-fold after intravenous and transdermal dosing in healthy and elde

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Luo, Xin, Zexin Zhang, Ruijing Mu, Guangyu Hu, Li Liu, and Xiaodong Liu. "Simultaneously Predicting the Pharmacokinetics of CES1-Metabolized Drugs and Their Metabolites Using Physiologically Based Pharmacokinetic Model in Cirrhosis Subjects." Pharmaceutics 16, no. 2 (2024): 234. http://dx.doi.org/10.3390/pharmaceutics16020234.

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Hepatic carboxylesterase 1 (CES1) metabolizes numerous prodrugs into active ingredients or direct-acting drugs into inactive metabolites. We aimed to develop a semi-physiologically based pharmacokinetic (semi-PBPK) model to simultaneously predict the pharmacokinetics of CES1 substrates and their active metabolites in liver cirrhosis (LC) patients. Six prodrugs (enalapril, benazepril, cilazapril, temocapril, perindopril and oseltamivir) and three direct-acting drugs (flumazenil, pethidine and remimazolam) were selected. Parameters such as organ blood flows, plasma-binding protein concentrations

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Lee, Jeong-Min, Jin-Ha Yoon, Han-Joo Maeng, and Yu Chul Kim. "Physiologically Based Pharmacokinetic (PBPK) Modeling to Predict CYP3A-Mediated Drug Interaction between Saxagliptin and Nicardipine: Bridging Rat-to-Human Extrapolation." Pharmaceutics 16, no. 2 (2024): 280. http://dx.doi.org/10.3390/pharmaceutics16020280.

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The aim of this study was to predict the cytochrome P450 3A (CYP3A)-mediated drug–drug interactions (DDIs) between saxagliptin and nicardipine using a physiologically based pharmacokinetic (PBPK) model. Initially, in silico and in vitro parameters were gathered from experiments or the literature to construct PBPK models for each drug in rats. These models were integrated to predict the DDIs between saxagliptin, metabolized via CYP3A2, and nicardipine, exhibiting CYP3A inhibitory activity. The rat DDI PBPK model was completed by optimizing parameters using experimental rat plasma concentrations

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Onasanwo, Anthonia M., Naresh Mittapelly, Laura Shireman, et al. "Using the Simcyp R Package for PBPK Simulation Workflows With the Simcyp Simulator." CPT: Pharmacometrics & Systems Pharmacology, April 3, 2025. https://doi.org/10.1002/psp4.70022.

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ABSTRACTPhysiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) modeling aims to understand how a drug is absorbed, distributed, metabolized, excreted, and acts in a human or animal body. The Simcyp Simulator is a well‐known commercial PBPK/PD simulation software offering many options. It can, for example, use multiple compounds and population specification files to study the behavior of specific drug formulations in particular population groups. Such features can greatly speed up and optimize clinical research and drug development studies. On the other hand, the statistical coding

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Rasool, Muhammad F., Shazia Ali, Sundus Khalid, et al. "Development and evaluation of physiologically based pharmacokinetic drug-disease models for predicting captopril pharmacokinetics in chronic diseases." Scientific Reports 11, no. 1 (2021). http://dx.doi.org/10.1038/s41598-021-88154-2.

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AbstractThe advancement in the processing speeds of computing machines has facilitated the development of complex physiologically based pharmacokinetic (PBPK) models. These PBPK models can incorporate disease-specific data and could be used to predict pharmacokinetics (PK) of administered drugs in different chronic conditions. The present study aimed to develop and evaluate PBPK drug-disease models for captopril after incorporating relevant pathophysiological changes occurring in adult chronic kidney disease (CKD) and chronic heart failure (CHF) populations. The population-based PBPK simulator

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Macente, Julia, Nina Nauwelaerts, Justine Marine Badée, et al. "Predicting Drug Transfer Into Human Milk With the Simcyp Simulator: A Contribution From the ConcePTION Project." CPT: Pharmacometrics & Systems Pharmacology, July 9, 2025. https://doi.org/10.1002/psp4.70066.

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ABSTRACTPhysiologically‐based pharmacokinetic (PBPK) modeling can support decision‐making on maternal medication use during breastfeeding. This study aimed to enhance lactation PBPK models in two ways. First, the utility of integrating permeability‐ versus perfusion‐limited distribution to human milk was explored using the Simcyp Simulator. Secondly, for permeability‐limited models, drug‐specific bidirectional intrinsic clearance across the blood‐milk barrier, predicted from drug physicochemical properties, was incorporated into lactation PBPK models. Initially, reference PBPK models were deve

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