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Pharmacokinetic and pharmacodynamic interaction of lorazepam and valproic acid in relation to UGT2B7 genetic polymorphism in healthy subjects

Cited 63 time in Web of Science Cited 68 time in Scopus
Authors
Chung, J-Y; Cho, J-Y; Yu, K-S; Kim, J-R; Lim, K S; Sohn, D-R; Shin, S-G; Jang, I-J
Issue Date
2007-08-10
Publisher
Elsevier
Citation
Clin Pharmacol Ther. 83(4):595-600
Keywords
AdultAnticonvulsants/administration & dosage/blood/pharmacokinetics/*pharmacologyArea Under CurveFemaleGlucuronosyltransferase/*geneticsHumansLorazepam/administration & dosage/blood/pharmacokinetics/*pharmacologyMale*Polymorphism, GeneticPsychometricsPsychomotor Performance/drug effectsValproic Acid/administration & dosage/blood/pharmacokinetics/*pharmacology
Abstract
Pharmacokinetic and pharmacodynamic profiles of lorazepam and valproate were analyzed according to uridine 5'-diphosphate-glucuronosyltransferase (UGT)2B7 genotype in 14 healthy subjects with UGT2B15*2/*2 genotype. Systemic clearance of lorazepam (2 mg intravenously) and area under the concentration-time curve (AUC) of valproate (600 mg once daily for 4 days) were analyzed as pharmacokinetic parameters, and area under the effect-time curve (AUEC) of psychomotor coordination tests (Vienna) was used for pharmacodynamic parameter. No significant differences were found in systemic clearances of lorazepam by UGT2B7 genotype. AUCs of valproate showed an increasing tendency as the number of UGT2B7*2 alleles increased, but the difference was insignificant. Psychometric results were significant among the UGT2B7 genotype group (AUEC_tracking 261.5+/-298.9 in *1/*1, and 3,396.8+/-947 in *2/*2, P=0.047) when the two drugs were coadministered. Our study suggests that the UGT2B7 genotype probably affects lorazepam-valproate pharmacodynamic interaction, especially in subjects who have homovariant genotypes of UGT2B7 and UGT2B15, although the effects on the pharmacokinetics are less significant.
ISSN
1532-6535 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17687269

http://www.nature.com/clpt/journal/v83/n4/pdf/6100324a.pdf

http://hdl.handle.net/10371/67797
DOI
https://doi.org/10.1038/sj.clpt.6100324
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College of Medicine/School of Medicine (의과대학/대학원)Pharmacology (약리학전공)Journal Papers (저널논문_약리학전공)
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