Evaluation of the single-dose pharmacokinetics and pharmacodynamics of apixaban in healthy Japanese and Caucasian subjects

Charles Frost,1 Andrew Shenker,1 Stanford Jhee,2 Zhigang Yu,1 Jessie Wang,3 Alexander Bragat,1 Janice Pursley,4 Frank LaCreta1 1Exploratory Clinical and Translational Research, Bristol-Myers Squibb, Princeton, NJ, USA; 2PAREXEL International Early Phase, Glendale, CA, USA; 3Exploratory Development G...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Frost C, Shenker A, Jhee S, Yu Z, Wang J, Bragat A, Pursley J, LaCreta F
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	safety pharmacokinetics pharmacodynamics Japanese apixaban anticoagulation Asian novel Eliquis Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/108edafcc5d147b8b447e1bf8b6c79f0
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:108edafcc5d147b8b447e1bf8b6c79f0
record_format	dspace
spelling	oai:doaj.org-article:108edafcc5d147b8b447e1bf8b6c79f02021-12-02T07:42:20ZEvaluation of the single-dose pharmacokinetics and pharmacodynamics of apixaban in healthy Japanese and Caucasian subjects1179-1438https://doaj.org/article/108edafcc5d147b8b447e1bf8b6c79f02018-10-01T00:00:00Zhttps://www.dovepress.com/evaluation-of-the-single-dose-pharmacokinetics-and-pharmacodynamics-of-peer-reviewed-article-CPAAhttps://doaj.org/toc/1179-1438Charles Frost,1 Andrew Shenker,1 Stanford Jhee,2 Zhigang Yu,1 Jessie Wang,3 Alexander Bragat,1 Janice Pursley,4 Frank LaCreta1 1Exploratory Clinical and Translational Research, Bristol-Myers Squibb, Princeton, NJ, USA; 2PAREXEL International Early Phase, Glendale, CA, USA; 3Exploratory Development Global Biometric Sciences, Bristol-Myers Squibb, Princeton, NJ, USA; 4Analytical and Bioanalytical Development, Bristol Myers Squibb, Princeton, NJ, USA Purpose: This double-blind, placebo-controlled, intra-subject, dose-escalation study assessed single-dose safety, pharmacokinetics, and pharmacodynamics of apixaban in healthy Japanese and Caucasian subjects. Subjects and methods: Sixteen healthy male Japanese and sixteen healthy male Caucasian subjects, matched for age, weight, and smoking status were randomized to receive four sequential single oral doses of either apixaban (2.5, 10, 25, and 50 mg) or matched placebo. Doses were separated by a ≥5-day washout. Blood samples were collected for the determination of apixaban plasma concentration, clotting times (international normalized ratio [INR], activated partial thromboplastin time, and modified prothrombin time [mPT]), and ex vivo thrombin generation (TG). Urine samples were collected for the analysis of apixaban concentration. Results: Ascending single doses of apixaban 2.5–50 mg were safe and well tolerated by all subjects. Apixaban exposure increased the dose proportionally up to 10 mg. Apixaban reached maximum concentrations (Cmax) 3–4 h postdose, with mean Cmax ranging from 52.5–485.0 to 44.8–494.3 ng/mL in Japanese and Caucasian subjects. The mean half-life was ~8 and ~13 h and the renal clearance was 1.1 and 0.8 L/h in Japanese and Caucasian subjects, respectively. Pharmacodynamic assessments were similar between ethnic groups, with comparable dose-related prolongation of INR and mPT and inhibition of TG. Conclusion: Ascending single doses of apixaban over a 20-fold dose range were safe and well tolerated in Japanese and Caucasian subjects in this study. The consistency between pharmacokinetic and pharmacodynamic measures in Japanese and Caucasian subjects indicates that apixaban may be administered as a fixed dose with no need for adjustment in Japanese patients. Keywords: safety, pharmacokinetics, pharmacodynamics, Japanese, apixaban, anticoagulation, Asian, novel, EliquisFrost CShenker AJhee SYu ZWang JBragat APursley JLaCreta FDove Medical PressarticlesafetypharmacokineticspharmacodynamicsJapaneseapixabananticoagulationAsiannovelEliquisTherapeutics. PharmacologyRM1-950ENClinical Pharmacology: Advances and Applications, Vol Volume 10, Pp 153-163 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	safety pharmacokinetics pharmacodynamics Japanese apixaban anticoagulation Asian novel Eliquis Therapeutics. Pharmacology RM1-950
spellingShingle	safety pharmacokinetics pharmacodynamics Japanese apixaban anticoagulation Asian novel Eliquis Therapeutics. Pharmacology RM1-950 Frost C Shenker A Jhee S Yu Z Wang J Bragat A Pursley J LaCreta F Evaluation of the single-dose pharmacokinetics and pharmacodynamics of apixaban in healthy Japanese and Caucasian subjects
description	Charles Frost,1 Andrew Shenker,1 Stanford Jhee,2 Zhigang Yu,1 Jessie Wang,3 Alexander Bragat,1 Janice Pursley,4 Frank LaCreta1 1Exploratory Clinical and Translational Research, Bristol-Myers Squibb, Princeton, NJ, USA; 2PAREXEL International Early Phase, Glendale, CA, USA; 3Exploratory Development Global Biometric Sciences, Bristol-Myers Squibb, Princeton, NJ, USA; 4Analytical and Bioanalytical Development, Bristol Myers Squibb, Princeton, NJ, USA Purpose: This double-blind, placebo-controlled, intra-subject, dose-escalation study assessed single-dose safety, pharmacokinetics, and pharmacodynamics of apixaban in healthy Japanese and Caucasian subjects. Subjects and methods: Sixteen healthy male Japanese and sixteen healthy male Caucasian subjects, matched for age, weight, and smoking status were randomized to receive four sequential single oral doses of either apixaban (2.5, 10, 25, and 50 mg) or matched placebo. Doses were separated by a ≥5-day washout. Blood samples were collected for the determination of apixaban plasma concentration, clotting times (international normalized ratio [INR], activated partial thromboplastin time, and modified prothrombin time [mPT]), and ex vivo thrombin generation (TG). Urine samples were collected for the analysis of apixaban concentration. Results: Ascending single doses of apixaban 2.5–50 mg were safe and well tolerated by all subjects. Apixaban exposure increased the dose proportionally up to 10 mg. Apixaban reached maximum concentrations (Cmax) 3–4 h postdose, with mean Cmax ranging from 52.5–485.0 to 44.8–494.3 ng/mL in Japanese and Caucasian subjects. The mean half-life was ~8 and ~13 h and the renal clearance was 1.1 and 0.8 L/h in Japanese and Caucasian subjects, respectively. Pharmacodynamic assessments were similar between ethnic groups, with comparable dose-related prolongation of INR and mPT and inhibition of TG. Conclusion: Ascending single doses of apixaban over a 20-fold dose range were safe and well tolerated in Japanese and Caucasian subjects in this study. The consistency between pharmacokinetic and pharmacodynamic measures in Japanese and Caucasian subjects indicates that apixaban may be administered as a fixed dose with no need for adjustment in Japanese patients. Keywords: safety, pharmacokinetics, pharmacodynamics, Japanese, apixaban, anticoagulation, Asian, novel, Eliquis
format	article
author	Frost C Shenker A Jhee S Yu Z Wang J Bragat A Pursley J LaCreta F
author_facet	Frost C Shenker A Jhee S Yu Z Wang J Bragat A Pursley J LaCreta F
author_sort	Frost C
title	Evaluation of the single-dose pharmacokinetics and pharmacodynamics of apixaban in healthy Japanese and Caucasian subjects
title_short	Evaluation of the single-dose pharmacokinetics and pharmacodynamics of apixaban in healthy Japanese and Caucasian subjects
title_full	Evaluation of the single-dose pharmacokinetics and pharmacodynamics of apixaban in healthy Japanese and Caucasian subjects
title_fullStr	Evaluation of the single-dose pharmacokinetics and pharmacodynamics of apixaban in healthy Japanese and Caucasian subjects
title_full_unstemmed	Evaluation of the single-dose pharmacokinetics and pharmacodynamics of apixaban in healthy Japanese and Caucasian subjects
title_sort	evaluation of the single-dose pharmacokinetics and pharmacodynamics of apixaban in healthy japanese and caucasian subjects
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/108edafcc5d147b8b447e1bf8b6c79f0
work_keys_str_mv	AT frostc evaluationofthesingledosepharmacokineticsandpharmacodynamicsofapixabaninhealthyjapaneseandcaucasiansubjects AT shenkera evaluationofthesingledosepharmacokineticsandpharmacodynamicsofapixabaninhealthyjapaneseandcaucasiansubjects AT jhees evaluationofthesingledosepharmacokineticsandpharmacodynamicsofapixabaninhealthyjapaneseandcaucasiansubjects AT yuz evaluationofthesingledosepharmacokineticsandpharmacodynamicsofapixabaninhealthyjapaneseandcaucasiansubjects AT wangj evaluationofthesingledosepharmacokineticsandpharmacodynamicsofapixabaninhealthyjapaneseandcaucasiansubjects AT bragata evaluationofthesingledosepharmacokineticsandpharmacodynamicsofapixabaninhealthyjapaneseandcaucasiansubjects AT pursleyj evaluationofthesingledosepharmacokineticsandpharmacodynamicsofapixabaninhealthyjapaneseandcaucasiansubjects AT lacretaf evaluationofthesingledosepharmacokineticsandpharmacodynamicsofapixabaninhealthyjapaneseandcaucasiansubjects
_version_	1718399201990148096

Evaluation of the single-dose pharmacokinetics and pharmacodynamics of apixaban in healthy Japanese and Caucasian subjects

Ejemplares similares