Single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy Chinese subjects

Yimin Cui,1 Yan Song,2 Jessie Wang,2 Zhigang Yu,2 Alan Schuster,2 Yu Chen Barrett,2 Charles Frost2 1Peking University First Hospital, Beijing, People's Republic of China; 2Bristol-Myers Squibb, Princeton, NJ, USA Background: The pharmacokinetics (PK), pharmacodynamics (PD), and safety of api...

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Autores principales:	Cui Y, Song Y, Wang J, Yu Z, Schuster A, Barrett YC, Frost C
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/2c90db79d39b4983b356b964f372d591
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spelling	oai:doaj.org-article:2c90db79d39b4983b356b964f372d5912021-12-02T01:15:07ZSingle- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy Chinese subjects1179-1438https://doaj.org/article/2c90db79d39b4983b356b964f372d5912013-12-01T00:00:00Zhttp://www.dovepress.com/single--and-multiple-dose-pharmacokinetics-pharmacodynamics-and-safety-a15212https://doaj.org/toc/1179-1438Yimin Cui,1 Yan Song,2 Jessie Wang,2 Zhigang Yu,2 Alan Schuster,2 Yu Chen Barrett,2 Charles Frost2 1Peking University First Hospital, Beijing, People's Republic of China; 2Bristol-Myers Squibb, Princeton, NJ, USA Background: The pharmacokinetics (PK), pharmacodynamics (PD), and safety of apixaban were assessed in healthy Chinese subjects in this randomized, placebo-controlled, double-blind, single-sequence, single- and multiple-dose study. Subjects and methods: Eighteen subjects 18–45 years of age were randomly assigned (2:1 ratio) to receive apixaban or matched placebo. Subjects received a single 10 mg dose of apixaban or placebo on day 1, followed by 10 mg apixaban or placebo twice daily for 6 days (days 4–9). The PK and PD of apixaban were assessed by collecting plasma samples for 72 hours following the dose on day 1 and the morning dose on day 9, and measuring apixaban concentration and anti-Xa activity. Safety was assessed via physical examinations, vital sign measurements, electrocardiograms, and clinical laboratory evaluations. Results: PK analysis showed similar characteristics of apixaban after single and multiple doses, including a median time to maximum concentration of ~3 hours, mean elimination half-life of ~11 hours, and renal clearance of ~1.2 L/hour. The accumulation index was 1.7, consistent with twice-daily dosing and the observed elimination half-life. Single-dose data predict multiple-dose PK, therefore apixaban PK are time-independent. The relationship between anti-Xa activity and plasma apixaban concentrations appears to be linear. Apixaban was safe and well tolerated, with no bleeding-related adverse events reported. Conclusion: Apixaban was safe and well tolerated in healthy Chinese subjects. Apixaban PK and PD were predictable and consistent with findings from previous studies in Asian and non-Asian subjects. The administration of apixaban does not require any dose modification based on race. Keywords: apixaban, oral anticoagulant, factor Xa inhibitor, pharmacokinetics, pharmacodynamicsCui YSong YWang JYu ZSchuster ABarrett YCFrost CDove Medical PressarticleTherapeutics. PharmacologyRM1-950ENClinical Pharmacology: Advances and Applications, Vol 2013, Iss Issue 1, Pp 177-184 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Therapeutics. Pharmacology RM1-950
spellingShingle	Therapeutics. Pharmacology RM1-950 Cui Y Song Y Wang J Yu Z Schuster A Barrett YC Frost C Single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy Chinese subjects
description	Yimin Cui,1 Yan Song,2 Jessie Wang,2 Zhigang Yu,2 Alan Schuster,2 Yu Chen Barrett,2 Charles Frost2 1Peking University First Hospital, Beijing, People's Republic of China; 2Bristol-Myers Squibb, Princeton, NJ, USA Background: The pharmacokinetics (PK), pharmacodynamics (PD), and safety of apixaban were assessed in healthy Chinese subjects in this randomized, placebo-controlled, double-blind, single-sequence, single- and multiple-dose study. Subjects and methods: Eighteen subjects 18–45 years of age were randomly assigned (2:1 ratio) to receive apixaban or matched placebo. Subjects received a single 10 mg dose of apixaban or placebo on day 1, followed by 10 mg apixaban or placebo twice daily for 6 days (days 4–9). The PK and PD of apixaban were assessed by collecting plasma samples for 72 hours following the dose on day 1 and the morning dose on day 9, and measuring apixaban concentration and anti-Xa activity. Safety was assessed via physical examinations, vital sign measurements, electrocardiograms, and clinical laboratory evaluations. Results: PK analysis showed similar characteristics of apixaban after single and multiple doses, including a median time to maximum concentration of ~3 hours, mean elimination half-life of ~11 hours, and renal clearance of ~1.2 L/hour. The accumulation index was 1.7, consistent with twice-daily dosing and the observed elimination half-life. Single-dose data predict multiple-dose PK, therefore apixaban PK are time-independent. The relationship between anti-Xa activity and plasma apixaban concentrations appears to be linear. Apixaban was safe and well tolerated, with no bleeding-related adverse events reported. Conclusion: Apixaban was safe and well tolerated in healthy Chinese subjects. Apixaban PK and PD were predictable and consistent with findings from previous studies in Asian and non-Asian subjects. The administration of apixaban does not require any dose modification based on race. Keywords: apixaban, oral anticoagulant, factor Xa inhibitor, pharmacokinetics, pharmacodynamics
format	article
author	Cui Y Song Y Wang J Yu Z Schuster A Barrett YC Frost C
author_facet	Cui Y Song Y Wang J Yu Z Schuster A Barrett YC Frost C
author_sort	Cui Y
title	Single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy Chinese subjects
title_short	Single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy Chinese subjects
title_full	Single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy Chinese subjects
title_fullStr	Single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy Chinese subjects
title_full_unstemmed	Single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy Chinese subjects
title_sort	single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy chinese subjects
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/2c90db79d39b4983b356b964f372d591
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Single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy Chinese subjects

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