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

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dc.contributor.authorChung, J-Y-
dc.contributor.authorCho, J-Y-
dc.contributor.authorYu, K-S-
dc.contributor.authorKim, J-R-
dc.contributor.authorLim, K S-
dc.contributor.authorSohn, D-R-
dc.contributor.authorShin, S-G-
dc.contributor.authorJang, I-J-
dc.date.accessioned2010-06-25T05:38:18Z-
dc.date.available2010-06-25T05:38:18Z-
dc.date.issued2007-08-10-
dc.identifier.citationClin Pharmacol Ther. 83(4):595-600en
dc.identifier.issn1532-6535 (Electronic)-
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17687269-
dc.identifier.urihttp://www.nature.com/clpt/journal/v83/n4/pdf/6100324a.pdf-
dc.identifier.urihttp://hdl.handle.net/10371/67797-
dc.description.abstractPharmacokinetic 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.en
dc.description.sponsorshipThis study was supported by a grant from the Korea Health 21 R&D
Project, Ministry of Health & Welfare, Republic of Korea (AO30001).
en
dc.language.isoen-
dc.publisherElsevieren
dc.subjectAdulten
dc.subjectAnticonvulsants/administration & dosage/blood/pharmacokinetics/*pharmacologyen
dc.subjectArea Under Curveen
dc.subjectFemaleen
dc.subjectGlucuronosyltransferase/*geneticsen
dc.subjectHumansen
dc.subjectLorazepam/administration & dosage/blood/pharmacokinetics/*pharmacologyen
dc.subjectMaleen
dc.subject*Polymorphism, Geneticen
dc.subjectPsychometricsen
dc.subjectPsychomotor Performance/drug effectsen
dc.subjectValproic Acid/administration & dosage/blood/pharmacokinetics/*pharmacologyen
dc.titlePharmacokinetic and pharmacodynamic interaction of lorazepam and valproic acid in relation to UGT2B7 genetic polymorphism in healthy subjectsen
dc.typeArticleen
dc.identifier.doi10.1038/sj.clpt.6100324-
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Pharmacology (약리학전공)Journal Papers (저널논문_약리학전공)
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