Academic literature on the topic 'Pidotimod'

A synthetic dipeptide, pidotimod (3-L-pyroglutamyl-L-thiaziolidine-4-carboxylic acid, PTD) is an immunomodulator and it possesses anti-infective activity against variety of infections. The objective of this study was to explore into and identify pidotimod’s major degradation product. Pidotimod was degraded in ICH prescribed stress conditions. pidotimod was degraded 90% in 1.0 N NaOH at 80 ºC for 6 h and the degradation product (DP2) was determined using HPLC. The HPLC method was used to separate the primary and subsidiary degradation products and carried out on a C18 column with a mobile phase of ammonium acetate buffer (pH 4.5; 10 mM) and MeOH/ACN (90:10 v/v) at a ratio of 97:03 v/v at 40 ºC, flow rate of 1.0 mL/min, and detection at 215 nm. IR, NMR and LC-MS-MS were used to identify degradation product (DP2) as 3,8-dihydroxy-tetrahydro-bisthiazolo[3,4,4a,3′,4′- d]pyrazine-5,10-dione.

The stability of pidotimod was investigated in this study under ICH-recommended stress degradation conditions. To explore the degradation kinetics of pidotimod, a QbD assisted stability indicating assay method was designed and validated according to ICH Q2 (R1) guidelines. The impacts of hydrogen and hydroxide ions were explored, with a focus on the kinetics of pidotimod hydrolytic degradation to identify the rate laws, which were parameterized using linear regression analysis. The degradation product (DP2) was formed as a major degradation product of hydrolysis. Four known and one unknown degradation product were formed under hydrolysis. Degradation of pidotimod in acid and base degradation follows first-order reaction kinetics while the neutral degradation follows zero-order reaction kinetics. The observed degradation products of pidotimod under hydrolytic degradation were identified by LC-MS/MS analysis and a mechanism of hydrolysis is proposed.

Background: The improvements in HIV infection therapy and the large availability of antiretroviral drugs have led to an increased survival among HIV infected people, and simultaneously to a raised morbidity and mortality due to not-AIDS-related events in this group compared to the general population. An increased systemic inflammation and a persistent immune activation play a pivotal role in determining high rates of non-AIDS comorbidities. In the last years, many natural or synthetic immunomodulatory molecules acting by different mechanisms have been conceived. Pidotimod is a synthetic dipeptide molecule showing immunomodulatory properties. The aim of this pilot study was to evaluate the effects of Pidotimod supplementation on residual inflammation in HIV infected population. Methods: Forty HIV positive individuals under cART were enrolled: 30 were treated with Pidotimod supplementation (study group) and 10 served as control group (without Pidotimod supplementation). For all participants, Cystatin C, PCR, ESR, microalbuminuria, TNF-α, INF-γ, IL-4, IL-10, IL1β, IL-18 and IL-2 were measured at enrolment (T0), 4 weeks after of Pidotimod supplementation (T1), and 4 weeks after completing supplementation (T2). Results: In HIV positive participants treated with Pidotimod, the evaluation of cytokine levels showed that IL-10, IFN gamma, and IL-4 were significantly higher at enrolment compared to the control group. The increase under Pidotimod treatment persisted after supplementation suspension, while the pro-inflammatory cytokines levels were reduced. Salivary IgA also increased during 4 weeks of supplementation and persisted at 4 weeks after completing supplementation. On the other hand, the Cystatin C and microalbuminuria levels decreased over time, at a greater extent the Cystatin C serum levels. Conclusions: The study findings showed that the HIV population receiving Pidotimod achieved a rebalancing of pro-inflammatory and anti-inflammatory cytokines as well as a significant reduction in cystatin C levels. The treatment further allowed for an increase in salivary IgA levels at all the analyzed times, as a secondary event to a remodulation of the immunological status obtained with pidotimod. This approach could represent a new way to design new intervention strategies aimed at improving the persistent immune activation status in the virologically suppressed HIV population.

Background: Recurrent respiratory infections (RRIs) are common in children especially in age 1 to 6 years. Pidotimod, an immunostimulant has been found to lower the recurrences of RRIs and improve the quality of life. The Objective of this study was to assess the efficacy and safety of pidotimod in children with recurrent respiratory infections (RRIs).Methods: In this single-centre, prospective, observational study, children aged 2 to 15 years diagnosed with RRIs were included. RRIs were defined as occurrence of 3 or more episodes of acute respiratory infections (ARIs) or more than 15 days of respiratory symptoms in the past 3 months. These children were treated with pidotimod in addition to standard care treatment. Treatment duration was two months and the follow-up continued for three months. Number of RRIs and severity of RRIs, antibiotic courses and rate of hospitalization before and after treatment were compared.Results: In total 25 children included in the study, mean age was 7.34±3.63 years. Among them, 68% were males. After treatment with pidotimod, there was significant reduction in mean number of ARI episodes (3.84±0.85 at baseline to 0.48±0.51 at follow-up, p<0.0001). Also, there was significant reduction in the duration of acute infectious episodes (p<0.0001), need of antibiotic courses (p<0.0001) and rates of hospitalization (p<0.0001). No safety concerns were identified and pidotimod was well tolerated.Conclusions: Addition of pidotimod to the standard treatment in children with RRIs significantly reduces the recurrence, duration of repeat infectious episodes, need of antibiotic treatments and future rates of hospitalizations. These findings support previous data.

Background: In recent years, the therapeutic options for COVID have significantly improved; however, the therapies are expensive with restricted access to drugs, and expeditious and difficult to manage at home. We investigated the effect of pidotimod in preventing hospitalization in patients with mild-moderate COVID-19. Methods: A total of 1231 patients between January and June 2021 were screened. A total of 184 patients with mild-moderate COVID-19 were enrolled and divided into two groups: group-A (97) had undergone therapy with pidotimod 800 mg bid for 7–10 days and group-B (87) had other therapies. We excluded those who had undergone complete vaccination course, monoclonal anti-spike/antivirals or the co-administration of pidotimod-steroid. The primary outcome chosen was the emergency room, hospitalization, and deaths for COVID-related causes; the secondary outcome chosen was the duration of COVID-19 illness. Results: A total of 34 patients (18.5%) required hospital treatment, 11 in group-A and 23 in group-B (11.3% vs. 26.4%, p = 0.008). The median disease duration in group-A was 21 days (IQR 17–27) vs. 23 (IQR 20–31) in group-B (p = 0.005). Patients in the pidotimod group had higher SpO2 in the walking test (IQR 96–99% vs. IQR 93–98%, p = 0.01) and a lower need for steroid rescue therapy (11.5% vs. 60.9%, p < 0.001). Conclusions: In the first phase of disease, pidotimod can represent an effective, low-cost, weapon, without restrictions of use, that is able to prevent a second aggressive phase and promote faster virological recovery.

Covid-19 was the third leading cause of death in all of 2020, but in December 2020 and the beginning of 2021, the disease suddenly spiked and briefly became the number one cause of death in the United States (u.s.), particularly among those aged 35 years or older even though as of June 30, 2021, about 66% of adults in the u.s. have received at least one Covid-19 vaccine dose. At present, there is no drug to treat Covid-19 that can reduce the morbidity and mortality significantly, which has brought great panic to the society and scientific community. Antiviral agents and immune-modulating treatments are currently being trialed. Searches were conducted in PubMed, ScienceDirect, Google Academic, LitCovid, and MedRxiv for studies published from the beginning of 2000 through April 2021 that tested the clinical uses of pidotimod. Articles were selected prioritizing randomized clinical trials, systematic reviews, and clinical practice guidelines. Research results showed that Immunotherapy proved to be an effective method for fighting against similar viral infections to Covid-19 such as sars-cov, and Middle East respiratory syndrome coronavirus (mers-cov). studies aimed to dilucidated the mechanism of action of pidotimod, as well as randomized clinical trials that evaluate the security and utility of the drug are needed. In this scenario, the administration of Pidotimod could represent a potentially innovative strategy. In conclusion, in patients with Covid-19 without pneumonia, pidotimod could be considered an option, well-tolerated, and associated with a rapid reduction of systemic symptoms of the disease

Background and objectives: A new pandemic has emerged across the world:Covid-19. Covid-19 has affected hundreds of millions of people globally. To stop the spread of the virus and gain a mass immunity several vaccines have been developed. BNT162b2-mRNA-vaccine has been shown to be largely effective and is widely administered. However the vaccine is not free from adverse events that could discourage vaccination in many people. The aim was evaluated adverse effect and immunological effect after second dose of BNT162b2-mRNA-vaccine in a healthcare population that take Pidotimod versus control subjects. Methods: All nurses and doctors working in Covid-19 unit were proposed to participate, up to the enrollment of 30participants. 10 participants took Pidotimod 800mg bid orally fasting, from the fourth day before the second dose of the BNT162b2-mRNA-vaccine, for a total of six days. The remaining 20 participants did not take any therapy. We studied the differences in anti-SARS-CoV2 IgM and IgG levels and the difference of frequency of adverse events between the two groups Results: Although there was no significant difference in IgG production between the two groups, we found a lower frequency of vaccine adverse events in the group supplemented with pidotimod. Conclusions: This work demonstrates how pidotimod, despite not having a proven efficacy in increasing the production of antibodies, significantly reduces the adverse events described compared to people vaccinated without pidotimod supplementation. The results we described in this paper could encourage many more clinicians and people to vaccinate and gain the mass immunity needed to end this pandemic.

Introduzione: Il pidotimod (PDT) è una molecola dipeptidica di sintesi ad azione immunomodulante. Tale composto è studiato già da diversi anni con incoraggianti risultati a carico sia del sistema immunitario innato che adattativo. Studi in vitro ed in vivo ne hanno già dimostrato i benefici effetti nel trattamento di molte patologie. Col nostro studio abbiamo voluto porre l’accento sugli effetti del PDT associato alla terapia antibiotica standard in pazienti ospedalizzati per polmonite contratta in comunità (CAP). Metodi: 36 pazienti ospedalizzati per CAP, di cui 20 bambini e 16 adulti, sono stati arruolati nello studio secondo specifici criteri di inclusione. I pazienti sono stati suddivisi in due gruppi di trattamento, al primo è stato somministrato PDT associato alla terapia antibiotica standard, al secondo la sola terapia antibiotica. I campioni di sangue sono stati prelevati a diverse tempistiche, i bambini sono stati prelevati al momento dell’arruolamento (T0), a 3 e 5 giorni dall’ inizio della terapia (T3 e T5), e a 7 giorni dalla fine della somministrazione farmacologica (T21), Gli adulti sono stati invece prelevati al momento dell’arruolamento (T0), e rispettivamente a 1, 3, e 5 giorni dall’inizio della terapia (T1, T3, T5). Le PBMC sono state isolate da sangue periferico e stimolate in presenza di pneumococco. Dopo 3 ore di stimolazione una parte delle cellule è stata utilizzata per l’estrazione dell’RNA per la valutazione dell’espressione di specifici geni coinvolti nella risposta antibatterica; mentre dopo 18 ore di stimolazione le restanti cellule sono state marcate per le analisi citofluorimetriche. Risultati: I risultati ottenuti nei bambini hanno evidenziato un’azione del PDT su cellule denritiche, dove modula l’espressione di marker di attivazione e molecole costimolatorie quali HLA DRII, CD80 e CD86; e monociti, sui quali incrementa l’espressione del TLR2. Inoltre il gruppo trattato con PDT manifesta anche un’incremento nella secrezione di citochine proinfiammatorie TNFα e IL-12. Negli adulti è stato anche osservato un aumento nell’ espressione del TLR4 a livello dei monociti, mentre nessuna differenza è stata osservata nella secrezione delle citochine proinfiammatorie. In aggiunta, in entrambi i gruppi si è osservata una modulazione nell’ espressione di geni coinvolti nella risposta infiammatoria e antimicrobica. Conclusioni: Questi risultati confermano gli effetti immunomodulanti del PDT già descritti in letteratura, nonché i benefici della molecola associata alla terapia antibiotica standard nei pazienti affetti da CAP, grazie alla sua azione a livello dell’immunità innata.
Background: Several studies have been made about pidotimod (PDT) and encouraging results have been collected. PDT is a synthetic dipeptide molecule that seems to have immunomodulatory activity on both innate and adaptive responses. Until now, the effects of PDT on the immune system have only been studied in vivo after long-term administration to evaluate whether its immunomodulatory activity might prevent the development of infections. This study was planned to evaluate the immunomodulatory activity of PDT administered together with standard antibiotic therapy in patients hospitalized for communityacquired pneumonia (CAP). Methods: A total of 36 patients, including 20 children and 16 adults hospitalized for community-acquired pneumonia (CAP) were randomized at a 1:1 ratio to receive either standard antibiotics plus pidotimod (PDT) or standard antibiotics alone to evaluate the immunomodulatory activity of PDT. In Children blood samples for the evaluation of immunological parameters were draw at the time of recruitment before therapy administration (T0), at 3 and 5 days after the initiation of therapy (T3 and T5), and 7 days after the therapy ended (T21). While adults blood samples were taken at T0 before therapy administration, T1, T3 and T5 (respectively after 1, 3 and 5 days from the beginning of the therapy). Isolated PBMC were stimulated for 3 hours for gene expression analysis, and 18 hours for cytometric analysis. Results: Following pneumococcal polysaccharide stimulation, in both groups, the percentage of dendritic cells (DCs) expressing activation and costimulatory molecules was significantly higher in patients receiving PDT plus antibiotics than in the controls. A significant increase in tumor necrosis factor-α and/or interleukin-12 secretion and expression of toll like receptor 2 was observed in PDT-treated children compared with controls. In adults results shown an increase of both TLR2 and TLR4, whereas no consistent effects of pidotimod on IL12 producing immune cells could be detected, TNFα producing monocytes and DCs were robustly reduced in pidotimod patients. In the PDT-treated groups, mRNA expression of antimicrobial peptides and genes involved in the inflammatory response were also augmented in comparison with the controls. Conclusions: These results confirm that supplementation of antibiotic therapy with Pidotimod in patients with CAP results in a potentially beneficial modulation of innate immunity.

BACKGROUND: Many preschool children develop recurrent respiratory tract infections (RRI). Strategies to prevent RRI include the use of immunomodulators, as pidotimod or probiotics, but there is limited evidence on the clinical effects of the treatment, alone or combined, as well as on the changes of urine metabolic profile following it. OBJECTIVES. To investigate whether the treatment with pidotimod and/or bifidobacteria were associated with 1) a reduced morbidity related to RRI and 2) differences in the urine metabolic profile. MATERIALS AND METHODS: The study is a four-arm, exploratory, prospective, randomized, double-blinded, placebo-controlled clinical trial conducted during 2 autumn seasons, over the same three-months periods in 2 consecutive years. Children aged 3-6 years with RRI who attended the nursery school were enrolled and randomly assigned to one of the 4 arms to receive active medications or placebos for the first 10 days of each month for 4 consecutive months. Metabolomic analyses on urine samples collected before and after treatment were performed using mass spectrometry combined with ultra-performance liquid chromatography (UPLC-MS). RESULTS: Compared to the placebo group, children receiving pidotimod, alone or combined with bifidobacteria, had a significantly higher proportion of symptom-free days (p=0.02 and p=0.003, respectively) and a significantly lower percentage of days with common cold (p=0.004 and p=0.005, respectively). In those children, we also found relevant changes in the urine metabolomic profile compared to children receiving placebo. Furthermore, children treated with pidotimod alone showed a different metabolic profile compared to children treated with pidotimod plus bifidobacteria. On the other side, children receiving bifidobacteria alone did not show differences with respect to the placebo group in clinical outcomes or metabolomic profiles. CONCLUSIONS: this study shows that children with RRI treated with pidotimod have a better clinical outcome and a different metabolomics profile after treatment, compared to subject receiving placebo while patients treated only with bifidobacteria did not show any difference in clinical outcomes and metabolomic profile in comparison to the placebo group. The combined treatment (pidotimod plus bifidobacterium) did not modify the clinical outcome, but metabolomic analysis was able to reveal, going beyond the clinic, a different behavior for these two groups, suggesting a possible role for the microbiota composition in the underlying physiopathologic mechanism.
PRESUPPOSTI DELLO STUDIO: Le infezioni respiratorie ricorrenti (IRR) rappresentano una condizione molto diffusa; contribuiscono in modo sostanziale alla morbilità pediatrica ed hanno un costo economico e sociale elevato. Gli immunostimolanti, come il pidotimod, sono utilizzati per la loro prevenzione. Recenti evidenze suggeriscono che anche i probiotici possano avere un ruolo preventivo nelle IRR. OBIETTIVO DELLO STUDIO: Valutare se il trattamento con pidotimod e/o bifidobatteri si associ a 1) riduzione della morbilità correlata alle IRR e 2) differenze nel profilo metabolomico urinario pre e post terapia MATERIALI E METODI: Si tratta di uno studio a 4 braccia, esplorativo, prospettico, randomizzato e controllato, in doppio cieco e versus placebo condotto durante gli stessi 3 mesi autunnali in due anni consecutivi. Sono stati arruolati bambini dai 3 ai 6 anni con diagnosi di IRR che frequentavano la scuola materna e sono stati assegnati in modo randomizzato a ricevere il trattamento attivo (pidotimod e/o bifidobatterio) o il placebo per i primi 10 giorni di ciascun mese per 4 mesi. L’analisi metabolomica sui campioni di urine raccolti prima e dopo il trattamento è stata eseguita mediante spettroscopia di massa accoppiata con cromatografia liquida ad alta performance (UPLC-MS). RISULTATI: Confrontati con il gruppo placebo, i bambini trattati con pidotimod, con o senza bifidobatteri, presentavano una proporzione di giorni liberi da sintomi significativamente più alta (p=0.02 and p=0.003, rispettivamente) e una percentuale più bassa di giorni con rinite (p=0.004 and p=0.005, rispettivamente). Dal punto di vista metabolomico questi bambini presentavano un profilo significativamente diverso rispetto a quelli trattati con placebo. I bambini trattati con solo pidotimod dimostravano un profilo metabolico urinario ancora diverso rispetto a quelli trattati con la combinazione pidotimod e bifidobatterio. Dall’altro lato i bambini trattati con solo bifidobatterio non dimostravano differenze significative se confrontati con il gruppo placebo né per quanto riguarda gli outcome clinici né nel profilo metabolomico. CONCLUSIONI: lo studio dimostra che i bambini con IRR trattati con pidotimod hanno un outcome clinico migliore e un profilo metabolomico urinario diverso rispetto ai bambini trattati con placebo, mentre i bambini trattati con il solo bifidobatterio non hanno dimostrato differenze né negli outcome clinici né nel profilo metabolomico se confrontati con quelli che hanno assunto placebo. L’associazione del bifidobatterio al pidotimod non modifica l’outcome clinico, ma l’analisi metabolomica è stata in grado di dimostrare, andando oltre la clinica, che questi due gruppi presentano delle differenze a cui la composizione del microbiota intestinale potrebbe contribuire.