Academic Journal
Single‐ and multiple‐dose pharmacokinetics and safety of pimodivir, a novel, non‐nucleoside polymerase basic protein 2 subunit inhibitor of the influenza A virus polymerase complex, and interaction with oseltamivir: a Phase 1 open‐label study in healthy volunteers
| العنوان: | Single‐ and multiple‐dose pharmacokinetics and safety of pimodivir, a novel, non‐nucleoside polymerase basic protein 2 subunit inhibitor of the influenza A virus polymerase complex, and interaction with oseltamivir: a Phase 1 open‐label study in healthy volunteers |
|---|---|
| المؤلفون: | Deleu, Sofie, Kakuda, Thomas N., Spittaels, Kurt, Vercauteren, Jurgen J., Hillewaert, Vera, Lwin, Amy, Leopold, Lorant, Hoetelmans, Richard M. W. |
| المساهمون: | Janssen Pharmaceuticals, NJ, USA |
| المصدر: | British Journal of Clinical Pharmacology ; volume 84, issue 11, page 2663-2672 ; ISSN 0306-5251 1365-2125 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2018 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | Aims The aim of this study was to evaluate the drug–drug interaction between pimodivir, a novel, non‐nucleoside polymerase basic protein 2 (PB2) subunit inhibitor of the influenza A virus polymerase complex, and oseltamivir, to assess the feasibility of this combination therapy. Furthermore, single‐ and multiple‐dose pharmacokinetics and safety of pimodivir in healthy volunteers were assessed. Methods In Part 1 of this open‐label Phase 1 study, healthy volunteers ( n = 18) were randomized to one of six cross‐over treatment sequences, each comprising administration of oseltamivir 75 mg or pimodivir 600 mg or combination thereof twice daily on Days 1–4, followed by a single morning dose on Day 5. Between each treatment session, there was a minimum 5‐day washout period. In Part 2, healthy volunteers ( n = 16) randomly received pimodivir 600 mg or placebo (3:1) twice daily on Days 1–9, followed by a single morning dose on Day 10. Pharmacokinetics of pimodivir, oseltamivir and oseltamivir carboxylate, and safety were assessed. Results In Part 1, co‐administration of pimodivir with oseltamivir increased the C max of pimodivir by 31% (90% CI: 0.92–1.85) with no change in C min or AUC 12h . Pimodivir had no effect on oseltamivir or oseltamivir carboxylate pharmacokinetics. In Part 2, after single‐ and multiple‐dose administration of pimodivir, there was a 1.2‐ and 1.8‐fold increase in C max and AUC 12h , respectively, between Day 1 and Day 10. The most frequently reported treatment‐emergent adverse event was diarrhoea ( n = 7 each in Part 1 and 2). Conclusion Combination treatment with pimodivir and oseltamivir in healthy volunteers showed no clinically relevant drug–drug interactions. No safety concerns were identified with pimodivir 600 mg twice daily alone or in combination with oseltamivir 75 mg twice daily. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1111/bcp.13733 |
| الاتاحة: | http://dx.doi.org/10.1111/bcp.13733 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fbcp.13733 https://onlinelibrary.wiley.com/doi/pdf/10.1111/bcp.13733 https://onlinelibrary.wiley.com/doi/full-xml/10.1111/bcp.13733 https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/bcp.13733 |
| Rights: | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| رقم الانضمام: | edsbas.55E9D533 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1111/bcp.13733 |
|---|