Pharmacokinetic and pharmacodynamic interaction of lorazepam and valproic acid in relation to UGT2B7 genetic polymorphism in healthy subjects.
Article Details
- CitationCopy to clipboard
Chung JY, Cho JY, Yu KS, Kim JR, Lim KS, Sohn DR, Shin SG, Jang IJ
Pharmacokinetic and pharmacodynamic interaction of lorazepam and valproic acid in relation to UGT2B7 genetic polymorphism in healthy subjects.
Clin Pharmacol Ther. 2008 Apr;83(4):595-600. Epub 2007 Aug 8.
- PubMed ID
- 17687269 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Valproic acid UDP-glucuronosyltransferase 1-3 Protein Humans UnknownSubstrateDetails Valproic acid UDP-glucuronosyltransferase 2B15 Protein Humans UnknownSubstrateDetails Valproic acid UDP-glucuronosyltransferase 2B7 Protein Humans UnknownSubstrateDetails