| Effects of CYP2C19 and CYP2C9 genotypes on pharmacokinetic variability of valproic acid in Chinese epileptic patients: nonlinear mixed-effect modeling. | |
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MedLine Citation:
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PMID: 19756559 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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PURPOSE: To evaluate the effects of CYP2C19 and CYP2C9 genotypes on the pharmacokinetic variability of valproic acid (VPA) in epileptic patients using a population pharmacokinetic (PPK) approach. METHODS: VPA concentrations were measured in 287 epileptic patients, who were genotyped for CYP2C19*2/*3 and CYP2C9*3. Patients who were on monotherapy with VPA were divided into two groups, a PPK-model group (n = 177) and a PPK-valid group (n = 110). The PPK parameter values for VPA were calculated in the PPK-model group by using the NONMEM software. Ultimately, a biological model and a final model were established. Each model was then used to independently predict the concentrations of the PPK-valid group to validate the two models. RESULTS: There was a significant effect of the CYP2C19 and CYP2C9 genotypes on the pharmacokinetic (PK) variability (P < 0.01) in the final PPK model of CL/F. The interindividual CL was calculated according to the final model: CL/F = 0.0951 x (1 + e(0.0267 x (3 - genotype))) + 0.0071 x age (L/h). The coefficient of variation (CV) (omega CL/F) of the final model was 29.3%, while that of the biological model was 31.7%. Based on the genotype, the individual PK parameters can be calculated more accurately than before. CONCLUSION: The CYP2C19 and CYP2C9 genotypes significantly influenced the PK variability of VPA, as quantified by NONMEM software. |
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Authors:
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Dechun Jiang; Xiangrong Bai; Qingxia Zhang; Wei Lu; Yuqin Wang; Lin Li; Markus Müller |
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Publication Detail:
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Type: Journal Article Date: 2009-09-16 |
Journal Detail:
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Title: European journal of clinical pharmacology Volume: 65 ISSN: 1432-1041 ISO Abbreviation: Eur. J. Clin. Pharmacol. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2010-01-21 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1256165 Medline TA: Eur J Clin Pharmacol Country: Germany |
Other Details:
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Languages: eng Pagination: 1187-93 Citation Subset: IM |
Affiliation:
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Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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