NDLI: Sex related differences on valproic acid pharmacokinetics after oral single dose

Content Provider	Springer Nature Link
Author	Ibarra, Manuel Vázquez, Marta Fagioli, Pietro Derendorf, Hartmut
Copyright Year	2013
Abstract	Plasma concentration–time data obtained after an oral single dose of 500-mg valproic acid (VPA) in a delayed release formulation was used to model enterohepatic cycling of the drug. Fourteen healthy subjects (seven women and seven men) were enrolled, food intake was standardized, blood samples were withdrawn up to 48 h post dosing and VPA plasma concentrations were analyzed by HPLC–UV method. Secondary peaks of VPA were observed in almost all subjects. A population pharmacokinetic analysis with sex, weight, age and contraceptive therapy as possible covariates was performed. Women without contraceptive therapy presented a longer lag time, a lower VPA hepatic output and a higher reabsorbed fraction than men. Weight affected both volume of the central compartment and the absorption rate constant. Women under contraceptive therapy showed similar disposition parameters to men. Reabsorbed fraction of bioavailable dose was 46.2 % in women and 21.8 % in men, revealing important sex differences in drug hepatobiliar output. These results showed that VPA displays sex-related pharmacokinetic differences due to different metabolic and transporter-mediated disposition.
Starting Page	479
Ending Page	486
Page Count	8
File Format	PDF
ISSN	1567567X
Journal	Journal of Pharmacokinetics and Pharmacodynamics
Volume Number	40
Issue Number	4
e-ISSN	15738744
Language	English
Publisher	Springer US
Publisher Date	2013-06-20
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Valproic acid Sex differences Pharmacokinetics Enterohepatic cycling Efflux transporters Pharmacology/Toxicology Pharmacy Veterinary Medicine Biomedical Engineering Biochemistry
Content Type	Text
Resource Type	Article
Subject	Pharmacology

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