tetano
Editor, Senior Moderator
Br J Clin Pharmacol. 2018 Aug 11. doi: 10.1111/bcp.13733. [Epub ahead of print]
[h=1]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.[/h] Deleu S[SUP]1[/SUP], Kakuda TN[SUP]2[/SUP], Spittaels K[SUP]3[/SUP], Vercauteren JJ[SUP]1[/SUP], Hillewaert V[SUP]1[/SUP], Lwin A[SUP]4[/SUP], Leopold L[SUP]5[/SUP], Hoetelmans RMW[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]AIM:[/h] 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.
[h=4]METHODS:[/h] In Part 1 of this open-label phase 1 study, healthy volunteers (n=18) were randomized to 1 of 6 cross-over treatment sequences, each comprising of oseltamivir 75-mg or pimodivir 600-mg or combination administered 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.
[h=4]RESULTS:[/h] In Part 1, co-administration of pimodivir with oseltamivir increased the C[SUB]max[/SUB] of pimodivir by 31% (90%CI: 0.92-1.85) with no change in C[SUB]min[/SUB] orAUC[SUB]12h[/SUB] . 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[SUB]max[/SUB] and AUC[SUB]12h[/SUB] , respectively, between day 1 and 10. The most frequently reported treatment-emergent adverse event was diarrhea (n=7 each in Part 1 and 2).
[h=4]CONCLUSION:[/h] 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.
This article is protected by copyright. All rights reserved.
[h=4]KEYWORDS:[/h] Combination; drug-drug interaction; oseltamivir; pharmacokinetics; pimodivir; safety
PMID: 30098042 DOI: 10.1111/bcp.13733
[h=1]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.[/h] Deleu S[SUP]1[/SUP], Kakuda TN[SUP]2[/SUP], Spittaels K[SUP]3[/SUP], Vercauteren JJ[SUP]1[/SUP], Hillewaert V[SUP]1[/SUP], Lwin A[SUP]4[/SUP], Leopold L[SUP]5[/SUP], Hoetelmans RMW[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]AIM:[/h] 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.
[h=4]METHODS:[/h] In Part 1 of this open-label phase 1 study, healthy volunteers (n=18) were randomized to 1 of 6 cross-over treatment sequences, each comprising of oseltamivir 75-mg or pimodivir 600-mg or combination administered 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.
[h=4]RESULTS:[/h] In Part 1, co-administration of pimodivir with oseltamivir increased the C[SUB]max[/SUB] of pimodivir by 31% (90%CI: 0.92-1.85) with no change in C[SUB]min[/SUB] orAUC[SUB]12h[/SUB] . 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[SUB]max[/SUB] and AUC[SUB]12h[/SUB] , respectively, between day 1 and 10. The most frequently reported treatment-emergent adverse event was diarrhea (n=7 each in Part 1 and 2).
[h=4]CONCLUSION:[/h] 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.
This article is protected by copyright. All rights reserved.
[h=4]KEYWORDS:[/h] Combination; drug-drug interaction; oseltamivir; pharmacokinetics; pimodivir; safety
PMID: 30098042 DOI: 10.1111/bcp.13733