tetano
Editor, Senior Moderator
J Pharm Sci. 2018 Dec 14. pii: S0022-3549(18)30800-1. doi: 10.1016/j.xphs.2018.12.005. [Epub ahead of print]
[h=1]Population Pharmacokinetic and Exposure-Response Analyses of Baloxavir Marboxil in Adults and Adolescents Including Influenza Patients.[/h] Koshimichi H[SUP]1[/SUP], Tsuda Y[SUP]1[/SUP], Ishibashi T[SUP]2[/SUP], Wajima T[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]PURPOSE:[/h] Baloxavir marboxil, a prodrug that is metabolized to baloxavir acid, suppresses viral replication by inhibiting cap-dependent endonuclease. Our aim is to characterize its pharmacokinetics and exposure-response relationships.
[h=4]METHODS:[/h] Population pharmacokinetic analysis of baloxavir acid was performed using 8310 plasma concentration data points from 1109 subjects. Exposure-response analyses were performed regarding the time to alleviation of symptoms and the reduction in the influenza virus titer.
[h=4]RESULTS:[/h] A two-compartment model with first-order absorption and lag time well described the plasma concentration data for baloxavir acid, and body weight and race were found to be the most important factors influencing clearance and distribution volume. A dose regimen based on body weight (40 mg for patients weighing < 80 kg and 80 mg for patients weighing ≥ 80 kg) could provide sufficient exposures for expecting efficacy irrespective of body weight or race, although the exposures were dependent on body weight and race. Exposure-response analyses suggested that the reduction in the influenza virus titer was greater in any exposure-based groups in baloxavir marboxil treatment than in the oseltamivir phosphate treatment and placebo groups.
[h=4]CONCLUSION:[/h] The population pharmacokinetic model and exposure-response relationships would be useful for understanding the pharmacokinetic and pharmacodynamic characteristics of baloxavir acid.
Copyright ? 2018. Published by Elsevier Inc.
[h=4]KEYWORDS:[/h] Baloxavir marboxil; S-033188; cap-dependent endonuclease inhibitor; influenza; population pharmacokinetics
PMID: 30557562 DOI: 10.1016/j.xphs.2018.12.005
[h=1]Population Pharmacokinetic and Exposure-Response Analyses of Baloxavir Marboxil in Adults and Adolescents Including Influenza Patients.[/h] Koshimichi H[SUP]1[/SUP], Tsuda Y[SUP]1[/SUP], Ishibashi T[SUP]2[/SUP], Wajima T[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]PURPOSE:[/h] Baloxavir marboxil, a prodrug that is metabolized to baloxavir acid, suppresses viral replication by inhibiting cap-dependent endonuclease. Our aim is to characterize its pharmacokinetics and exposure-response relationships.
[h=4]METHODS:[/h] Population pharmacokinetic analysis of baloxavir acid was performed using 8310 plasma concentration data points from 1109 subjects. Exposure-response analyses were performed regarding the time to alleviation of symptoms and the reduction in the influenza virus titer.
[h=4]RESULTS:[/h] A two-compartment model with first-order absorption and lag time well described the plasma concentration data for baloxavir acid, and body weight and race were found to be the most important factors influencing clearance and distribution volume. A dose regimen based on body weight (40 mg for patients weighing < 80 kg and 80 mg for patients weighing ≥ 80 kg) could provide sufficient exposures for expecting efficacy irrespective of body weight or race, although the exposures were dependent on body weight and race. Exposure-response analyses suggested that the reduction in the influenza virus titer was greater in any exposure-based groups in baloxavir marboxil treatment than in the oseltamivir phosphate treatment and placebo groups.
[h=4]CONCLUSION:[/h] The population pharmacokinetic model and exposure-response relationships would be useful for understanding the pharmacokinetic and pharmacodynamic characteristics of baloxavir acid.
Copyright ? 2018. Published by Elsevier Inc.
[h=4]KEYWORDS:[/h] Baloxavir marboxil; S-033188; cap-dependent endonuclease inhibitor; influenza; population pharmacokinetics
PMID: 30557562 DOI: 10.1016/j.xphs.2018.12.005