tetano
Editor, Senior Moderator
Clin Drug Investig. 2018 Oct 4. doi: 10.1007/s40261-018-0710-9. [Epub ahead of print]
[h=1]Safety, Tolerability, and Pharmacokinetics of the Novel Anti-influenza Agent Baloxavir Marboxil in Healthy Adults: Phase I Study Findings.[/h] Koshimichi H[SUP]1[/SUP], Ishibashi T[SUP]2[/SUP], Kawaguchi N[SUP]1[/SUP], Sato C[SUP]3[/SUP], Kawasaki A[SUP]4[/SUP], Wajima T[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND AND OBJECTIVE:[/h] Baloxavir marboxil, a prodrug that is metabolized to baloxavir acid, suppresses viral replication by inhibiting cap-dependent endonuclease. This first-in-human phase I study evaluated the safety, tolerability, and pharmacokinetics of baloxavir marboxil/baloxavir acid in healthy Japanese volunteers (Study 1), while food effects were evaluated in a separate phase I, crossover study in healthy Japanese volunteers (Study 2).
[h=4]METHODS:[/h] Study 1 participants were randomized to single-dose oral baloxavir marboxil (6, 20, 40, 60, or 80 mg; n = 6 per dose) or placebo (n = 10), while Study 2 participants (n = 15) received single-dose oral baloxavir marboxil 20 mg in fasted, fed, and before-meal states.
[h=4]RESULTS:[/h] Baloxavir marboxil was well tolerated; there were few treatment-emergent adverse events and no serious adverse events/deaths. The mean plasma baloxavir acid concentration 24 h after single-dose (C[SUB]24[/SUB]) oral baloxavir marboxil 6 mg was 6.92 ng/mL, exceeding the target C[SUB]24[/SUB] (6.85 ng/mL) estimated in nonclinical studies. In Study 1, baloxavir acid exposure demonstrated dose-proportional increases in the fasted state, with maximum plasma concentration generally attained within 3.5 h. Terminal elimination half-life ranged from 49 to 91 h. In Study 2, exposure was decreased and apparent clearance increased in the fed and before-meal states versus the fasted state; however, exposure exceeded the target C[SUB]24[/SUB] in all states.
[h=4]CONCLUSION:[/h] Single-dose oral baloxavir marboxil was well tolerated, had a favorable safety profile, and had favorable pharmacokinetic characteristics, including a long half-life, supporting single oral dosing. The baloxavir acid area under the plasma concentration-time curve decreased with food intake by approximately 40%.
PMID: 30288682 DOI: 10.1007/s40261-018-0710-9
[h=1]Safety, Tolerability, and Pharmacokinetics of the Novel Anti-influenza Agent Baloxavir Marboxil in Healthy Adults: Phase I Study Findings.[/h] Koshimichi H[SUP]1[/SUP], Ishibashi T[SUP]2[/SUP], Kawaguchi N[SUP]1[/SUP], Sato C[SUP]3[/SUP], Kawasaki A[SUP]4[/SUP], Wajima T[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND AND OBJECTIVE:[/h] Baloxavir marboxil, a prodrug that is metabolized to baloxavir acid, suppresses viral replication by inhibiting cap-dependent endonuclease. This first-in-human phase I study evaluated the safety, tolerability, and pharmacokinetics of baloxavir marboxil/baloxavir acid in healthy Japanese volunteers (Study 1), while food effects were evaluated in a separate phase I, crossover study in healthy Japanese volunteers (Study 2).
[h=4]METHODS:[/h] Study 1 participants were randomized to single-dose oral baloxavir marboxil (6, 20, 40, 60, or 80 mg; n = 6 per dose) or placebo (n = 10), while Study 2 participants (n = 15) received single-dose oral baloxavir marboxil 20 mg in fasted, fed, and before-meal states.
[h=4]RESULTS:[/h] Baloxavir marboxil was well tolerated; there were few treatment-emergent adverse events and no serious adverse events/deaths. The mean plasma baloxavir acid concentration 24 h after single-dose (C[SUB]24[/SUB]) oral baloxavir marboxil 6 mg was 6.92 ng/mL, exceeding the target C[SUB]24[/SUB] (6.85 ng/mL) estimated in nonclinical studies. In Study 1, baloxavir acid exposure demonstrated dose-proportional increases in the fasted state, with maximum plasma concentration generally attained within 3.5 h. Terminal elimination half-life ranged from 49 to 91 h. In Study 2, exposure was decreased and apparent clearance increased in the fed and before-meal states versus the fasted state; however, exposure exceeded the target C[SUB]24[/SUB] in all states.
[h=4]CONCLUSION:[/h] Single-dose oral baloxavir marboxil was well tolerated, had a favorable safety profile, and had favorable pharmacokinetic characteristics, including a long half-life, supporting single oral dosing. The baloxavir acid area under the plasma concentration-time curve decreased with food intake by approximately 40%.
PMID: 30288682 DOI: 10.1007/s40261-018-0710-9