Population pharmacokinetics of olprinone in healthy male volunteers

Takayuki Kunisawa,1 Hidefumi Kasai,2 Makoto Suda,2 Manabu Yoshimura,3 Ami Sugawara,3 Yuki Izumi,3 Takafumi Iida,3 Atsushi Kurosawa,3 Hiroshi Iwasaki3 1Surgical Operation Department, Asahikawa Medical University Hospital, Hokkaido, Japan; 2Clinical Study Management Division, Bell Medical Solutions I...

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Autores principales:	Kunisawa T, Kasai H, Suda M, Yoshimura M, Sugawara A, Izumi Y, Iida T, Kurosawa A, Iwasaki H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/00566222cb6d4f0dab4aaa3c70fac0c1
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spelling	oai:doaj.org-article:00566222cb6d4f0dab4aaa3c70fac0c12021-12-02T06:37:35ZPopulation pharmacokinetics of olprinone in healthy male volunteers1179-1438https://doaj.org/article/00566222cb6d4f0dab4aaa3c70fac0c12014-03-01T00:00:00Zhttp://www.dovepress.com/population-pharmacokinetics-of-olprinone-in-healthy-male-volunteers-a16002https://doaj.org/toc/1179-1438 Takayuki Kunisawa,1 Hidefumi Kasai,2 Makoto Suda,2 Manabu Yoshimura,3 Ami Sugawara,3 Yuki Izumi,3 Takafumi Iida,3 Atsushi Kurosawa,3 Hiroshi Iwasaki3 1Surgical Operation Department, Asahikawa Medical University Hospital, Hokkaido, Japan; 2Clinical Study Management Division, Bell Medical Solutions Inc, Tokyo, Japan; 3Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Hokkaido, Japan Background: Olprinone decreases the cardiac preload and/or afterload because of its vasodilatory effect and increases myocardial contractility by inhibiting phosphodiesterase III. Purpose: The objective of this study was to characterize the population pharmacokinetics of olprinone after a single continuous infusion in healthy male volunteers. Methods: We used 500 plasma concentration data points collected from nine healthy male volunteers for the study. The population pharmacokinetic analysis was performed using the nonlinear mixed effect model (NONMEM®) software. Results: The time course of plasma concentration of olprinone was best described using a two-compartment model. The final pharmacokinetic parameters were total clearance (7.37 mL/minute/kg), distribution volume of the central compartment (134 mL/kg), intercompartmental clearance (7.75 mL/minute/kg), and distribution volume of the peripheral compartment (275 mL/kg). The interindividual variability in the total clearance was 12.4%, and the residual error variability (exponential and additive) were 22.2% and 0.129 (standard deviation). The final pharmacokinetic model was assessed using a bootstrap method and visual predictive check. Conclusion: We developed a population pharmacokinetic model of olprinone in healthy male adults. The bootstrap method and visual predictive check showed that this model was appropriate. Our results might be used to develop the population pharmacokinetic model in patients. Keywords: phosphodiesterase III inhibitor, men, pharmacokinetic modelKunisawa TKasai HSuda MYoshimura MSugawara AIzumi YIida TKurosawa AIwasaki HDove Medical PressarticleTherapeutics. PharmacologyRM1-950ENClinical Pharmacology: Advances and Applications, Vol 2014, Iss default, Pp 43-50 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Therapeutics. Pharmacology RM1-950
spellingShingle	Therapeutics. Pharmacology RM1-950 Kunisawa T Kasai H Suda M Yoshimura M Sugawara A Izumi Y Iida T Kurosawa A Iwasaki H Population pharmacokinetics of olprinone in healthy male volunteers
description	Takayuki Kunisawa,1 Hidefumi Kasai,2 Makoto Suda,2 Manabu Yoshimura,3 Ami Sugawara,3 Yuki Izumi,3 Takafumi Iida,3 Atsushi Kurosawa,3 Hiroshi Iwasaki3 1Surgical Operation Department, Asahikawa Medical University Hospital, Hokkaido, Japan; 2Clinical Study Management Division, Bell Medical Solutions Inc, Tokyo, Japan; 3Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Hokkaido, Japan Background: Olprinone decreases the cardiac preload and/or afterload because of its vasodilatory effect and increases myocardial contractility by inhibiting phosphodiesterase III. Purpose: The objective of this study was to characterize the population pharmacokinetics of olprinone after a single continuous infusion in healthy male volunteers. Methods: We used 500 plasma concentration data points collected from nine healthy male volunteers for the study. The population pharmacokinetic analysis was performed using the nonlinear mixed effect model (NONMEM®) software. Results: The time course of plasma concentration of olprinone was best described using a two-compartment model. The final pharmacokinetic parameters were total clearance (7.37 mL/minute/kg), distribution volume of the central compartment (134 mL/kg), intercompartmental clearance (7.75 mL/minute/kg), and distribution volume of the peripheral compartment (275 mL/kg). The interindividual variability in the total clearance was 12.4%, and the residual error variability (exponential and additive) were 22.2% and 0.129 (standard deviation). The final pharmacokinetic model was assessed using a bootstrap method and visual predictive check. Conclusion: We developed a population pharmacokinetic model of olprinone in healthy male adults. The bootstrap method and visual predictive check showed that this model was appropriate. Our results might be used to develop the population pharmacokinetic model in patients. Keywords: phosphodiesterase III inhibitor, men, pharmacokinetic model
format	article
author	Kunisawa T Kasai H Suda M Yoshimura M Sugawara A Izumi Y Iida T Kurosawa A Iwasaki H
author_facet	Kunisawa T Kasai H Suda M Yoshimura M Sugawara A Izumi Y Iida T Kurosawa A Iwasaki H
author_sort	Kunisawa T
title	Population pharmacokinetics of olprinone in healthy male volunteers
title_short	Population pharmacokinetics of olprinone in healthy male volunteers
title_full	Population pharmacokinetics of olprinone in healthy male volunteers
title_fullStr	Population pharmacokinetics of olprinone in healthy male volunteers
title_full_unstemmed	Population pharmacokinetics of olprinone in healthy male volunteers
title_sort	population pharmacokinetics of olprinone in healthy male volunteers
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/00566222cb6d4f0dab4aaa3c70fac0c1
work_keys_str_mv	AT kunisawat populationpharmacokineticsofolprinoneinhealthymalevolunteers AT kasaih populationpharmacokineticsofolprinoneinhealthymalevolunteers AT sudam populationpharmacokineticsofolprinoneinhealthymalevolunteers AT yoshimuram populationpharmacokineticsofolprinoneinhealthymalevolunteers AT sugawaraa populationpharmacokineticsofolprinoneinhealthymalevolunteers AT izumiy populationpharmacokineticsofolprinoneinhealthymalevolunteers AT iidat populationpharmacokineticsofolprinoneinhealthymalevolunteers AT kurosawaa populationpharmacokineticsofolprinoneinhealthymalevolunteers AT iwasakih populationpharmacokineticsofolprinoneinhealthymalevolunteers
_version_	1718399793354506240

Population pharmacokinetics of olprinone in healthy male volunteers

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