Effect of CYP3A4 metabolism on sex differences in the pharmacokinetics and pharmacodynamics of zolpidem

Abstract To investigate pharmacokinetic and pharmacodynamic differences of zolpidem between males and females and their causes, including CYP3A4 activity. A single oral dose of zolpidem (10 mg) was administered to 15 male and 15 female healthy subjects. Blood samples were collected up to 12 h post-d...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Seonghae Yoon, Seongmee Jeong, Eben Jung, Ki Soon Kim, Inseung Jeon, Yujin Lee, Joo-Youn Cho, Woo-Yong Oh, Jae-Yong Chung
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fe0b64a9a5ed40f9b2dfb8bd4e5dc839
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:fe0b64a9a5ed40f9b2dfb8bd4e5dc839
record_format	dspace
spelling	oai:doaj.org-article:fe0b64a9a5ed40f9b2dfb8bd4e5dc8392021-12-02T17:37:35ZEffect of CYP3A4 metabolism on sex differences in the pharmacokinetics and pharmacodynamics of zolpidem10.1038/s41598-021-98689-z2045-2322https://doaj.org/article/fe0b64a9a5ed40f9b2dfb8bd4e5dc8392021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98689-zhttps://doaj.org/toc/2045-2322Abstract To investigate pharmacokinetic and pharmacodynamic differences of zolpidem between males and females and their causes, including CYP3A4 activity. A single oral dose of zolpidem (10 mg) was administered to 15 male and 15 female healthy subjects. Blood samples were collected up to 12 h post-dose to determine plasma zolpidem concentrations. Pharmacokinetic parameters were obtained using non-compartmental analysis. Digit symbol substitution test, choice reaction time, and visual analog scale of sleepiness were used to evaluate pharmacodynamics. We measured CYP3A4 activity using 4β-hydroxycholesterol, an endogenous metabolite. Mean maximum plasma concentration and area under the plasma concentration–time curve were higher for females than for males (9.9% and 32.5%, respectively); other pharmacokinetic parameters showed no significant differences. Pharmacodynamic scores for females showed delayed recovery compared with that for males. CYP3A4 activity was higher in females than in males (p = 0.030). There was no serious adverse event, and adverse event incidence was not different between the sexes. Zolpidem exposure was about 30% higher in females than in males. Delayed pharmacodynamic score recovery in females could be related to higher zolpidem concentrations. Although apparent clearance was lower in females, systemic clearance might not be the cause of the different exposures to zolpidem.Seonghae YoonSeongmee JeongEben JungKi Soon KimInseung JeonYujin LeeJoo-Youn ChoWoo-Yong OhJae-Yong ChungNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Seonghae Yoon Seongmee Jeong Eben Jung Ki Soon Kim Inseung Jeon Yujin Lee Joo-Youn Cho Woo-Yong Oh Jae-Yong Chung Effect of CYP3A4 metabolism on sex differences in the pharmacokinetics and pharmacodynamics of zolpidem
description	Abstract To investigate pharmacokinetic and pharmacodynamic differences of zolpidem between males and females and their causes, including CYP3A4 activity. A single oral dose of zolpidem (10 mg) was administered to 15 male and 15 female healthy subjects. Blood samples were collected up to 12 h post-dose to determine plasma zolpidem concentrations. Pharmacokinetic parameters were obtained using non-compartmental analysis. Digit symbol substitution test, choice reaction time, and visual analog scale of sleepiness were used to evaluate pharmacodynamics. We measured CYP3A4 activity using 4β-hydroxycholesterol, an endogenous metabolite. Mean maximum plasma concentration and area under the plasma concentration–time curve were higher for females than for males (9.9% and 32.5%, respectively); other pharmacokinetic parameters showed no significant differences. Pharmacodynamic scores for females showed delayed recovery compared with that for males. CYP3A4 activity was higher in females than in males (p = 0.030). There was no serious adverse event, and adverse event incidence was not different between the sexes. Zolpidem exposure was about 30% higher in females than in males. Delayed pharmacodynamic score recovery in females could be related to higher zolpidem concentrations. Although apparent clearance was lower in females, systemic clearance might not be the cause of the different exposures to zolpidem.
format	article
author	Seonghae Yoon Seongmee Jeong Eben Jung Ki Soon Kim Inseung Jeon Yujin Lee Joo-Youn Cho Woo-Yong Oh Jae-Yong Chung
author_facet	Seonghae Yoon Seongmee Jeong Eben Jung Ki Soon Kim Inseung Jeon Yujin Lee Joo-Youn Cho Woo-Yong Oh Jae-Yong Chung
author_sort	Seonghae Yoon
title	Effect of CYP3A4 metabolism on sex differences in the pharmacokinetics and pharmacodynamics of zolpidem
title_short	Effect of CYP3A4 metabolism on sex differences in the pharmacokinetics and pharmacodynamics of zolpidem
title_full	Effect of CYP3A4 metabolism on sex differences in the pharmacokinetics and pharmacodynamics of zolpidem
title_fullStr	Effect of CYP3A4 metabolism on sex differences in the pharmacokinetics and pharmacodynamics of zolpidem
title_full_unstemmed	Effect of CYP3A4 metabolism on sex differences in the pharmacokinetics and pharmacodynamics of zolpidem
title_sort	effect of cyp3a4 metabolism on sex differences in the pharmacokinetics and pharmacodynamics of zolpidem
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/fe0b64a9a5ed40f9b2dfb8bd4e5dc839
work_keys_str_mv	AT seonghaeyoon effectofcyp3a4metabolismonsexdifferencesinthepharmacokineticsandpharmacodynamicsofzolpidem AT seongmeejeong effectofcyp3a4metabolismonsexdifferencesinthepharmacokineticsandpharmacodynamicsofzolpidem AT ebenjung effectofcyp3a4metabolismonsexdifferencesinthepharmacokineticsandpharmacodynamicsofzolpidem AT kisoonkim effectofcyp3a4metabolismonsexdifferencesinthepharmacokineticsandpharmacodynamicsofzolpidem AT inseungjeon effectofcyp3a4metabolismonsexdifferencesinthepharmacokineticsandpharmacodynamicsofzolpidem AT yujinlee effectofcyp3a4metabolismonsexdifferencesinthepharmacokineticsandpharmacodynamicsofzolpidem AT jooyouncho effectofcyp3a4metabolismonsexdifferencesinthepharmacokineticsandpharmacodynamicsofzolpidem AT wooyongoh effectofcyp3a4metabolismonsexdifferencesinthepharmacokineticsandpharmacodynamicsofzolpidem AT jaeyongchung effectofcyp3a4metabolismonsexdifferencesinthepharmacokineticsandpharmacodynamicsofzolpidem
_version_	1718379919497494528

Effect of CYP3A4 metabolism on sex differences in the pharmacokinetics and pharmacodynamics of zolpidem

Ejemplares similares