tetano
Editor, Senior Moderator
Clin Transl Sci
. 2022 Feb 17.
doi: 10.1111/cts.13237. Online ahead of print.
Pharmacokinetics, safety and simulated efficacy of an influenza treatment, baloxavir marboxil, in Chinese individuals
Yanmei Liu[SUP] 1 2 [/SUP], Sylvie Retout[SUP] 3 [/SUP], Vincent Duval[SUP] 4 [/SUP], Jingying Jia[SUP] 1 2 [/SUP], Yang Zou[SUP] 1 2 [/SUP], Yijun Wang[SUP] 1 2 [/SUP], Valérie Cosson[SUP] 3 [/SUP], Sébastien Jolivet[SUP] 3 [/SUP], Stefan De Buck[SUP] 3 [/SUP]
Affiliations
Abstract
Baloxavir marboxil is an endonuclease inhibitor indicated for the treatment of influenza in patients ≥12 years. No data exist for Chinese patients in global studies. This randomized, open-label, phase I study evaluated the pharmacokinetics (PK) and safety of baloxavir marboxil in healthy Chinese volunteers and was used to anticipate efficacy in Chinese patients. Patients received a single oral dose of baloxavir marboxil (40 or 80 mg [1:1]). Serial blood samples were collected pre-dose and at various time points up to 14 days post-dose. Baloxavir marboxil and acid plasma concentrations were determined by liquid chromatography tandem mass spectrometry. PK parameters of baloxavir acid were estimated by noncompartmental analysis. Adverse events (AEs) were recorded. Time to alleviation of symptoms (TTAS) was simulated for otherwise healthy (OwH) and high-risk (HR) Chinese and Asian patients. Thirty-two male patients received baloxavir marboxil. Baloxavir acid plasma concentration peaked 4 h post-dose. Mean C[SUB]max[/SUB] was 107.6 and 206.9 ng/ml, and mean AUC[SUB]0-inf[/SUB] was 6955 and 9643 ng·h/ml in the 40 and 80 mg cohorts, respectively. AEs were mild and transient; no new safety signals were identified. Simulated median TTAS for OwH and HR Chinese patients agreed with simulated values in Asian patients. PK parameters were similar to Asian populations in other studies. The globally adopted baloxavir marboxil dosing strategy was consistent with the established safety profile of baloxavir marboxil in this population. Simulated efficacy indicated Chinese patients could benefit from similar efficacy to Asian patients.
Keywords: anti-infective; pharmacokinetics; phase I; race.
. 2022 Feb 17.
doi: 10.1111/cts.13237. Online ahead of print.
Pharmacokinetics, safety and simulated efficacy of an influenza treatment, baloxavir marboxil, in Chinese individuals
Yanmei Liu[SUP] 1 2 [/SUP], Sylvie Retout[SUP] 3 [/SUP], Vincent Duval[SUP] 4 [/SUP], Jingying Jia[SUP] 1 2 [/SUP], Yang Zou[SUP] 1 2 [/SUP], Yijun Wang[SUP] 1 2 [/SUP], Valérie Cosson[SUP] 3 [/SUP], Sébastien Jolivet[SUP] 3 [/SUP], Stefan De Buck[SUP] 3 [/SUP]
Affiliations
- PMID: 35176206
- DOI: 10.1111/cts.13237
Abstract
Baloxavir marboxil is an endonuclease inhibitor indicated for the treatment of influenza in patients ≥12 years. No data exist for Chinese patients in global studies. This randomized, open-label, phase I study evaluated the pharmacokinetics (PK) and safety of baloxavir marboxil in healthy Chinese volunteers and was used to anticipate efficacy in Chinese patients. Patients received a single oral dose of baloxavir marboxil (40 or 80 mg [1:1]). Serial blood samples were collected pre-dose and at various time points up to 14 days post-dose. Baloxavir marboxil and acid plasma concentrations were determined by liquid chromatography tandem mass spectrometry. PK parameters of baloxavir acid were estimated by noncompartmental analysis. Adverse events (AEs) were recorded. Time to alleviation of symptoms (TTAS) was simulated for otherwise healthy (OwH) and high-risk (HR) Chinese and Asian patients. Thirty-two male patients received baloxavir marboxil. Baloxavir acid plasma concentration peaked 4 h post-dose. Mean C[SUB]max[/SUB] was 107.6 and 206.9 ng/ml, and mean AUC[SUB]0-inf[/SUB] was 6955 and 9643 ng·h/ml in the 40 and 80 mg cohorts, respectively. AEs were mild and transient; no new safety signals were identified. Simulated median TTAS for OwH and HR Chinese patients agreed with simulated values in Asian patients. PK parameters were similar to Asian populations in other studies. The globally adopted baloxavir marboxil dosing strategy was consistent with the established safety profile of baloxavir marboxil in this population. Simulated efficacy indicated Chinese patients could benefit from similar efficacy to Asian patients.
Keywords: anti-infective; pharmacokinetics; phase I; race.