| Effect of CYP2C19 genetic polymorphism on pharmacokinetics of phenytoin and phenobarbital in Japanese epileptic patients using Non-linear Mixed Effects Model approach. | |
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MedLine Citation:
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PMID: 16789993 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: To clarify the effect of genetic polymorphism of CYP2C19 on pharmacokinetics of phenytoin and phenobarbital using a Non-linear Mixed Effects Modelling analysis in Japanese epileptic patients. METHOD: A total of 326 serum phenytoin concentrations were collected from 132 patients, and a total of 144 serum phenobarbital concentrations were collected from 74 patients during their clinical routine care. RESULT: The maximal elimination rate of phenytoin decreased by 10.2% in patients with CYP2C19*1/*2 compared with patients with normal CYP2C19. The Michaelis-Menten constants in the patients with CYP2C19*1/*3 and the poor metabolizers of (CYP2C19*2/*2 or *2/*3 or *3/*3) were 27% and 54% higher than those for the patients with normal CYP2C19, respectively. The total body clearance of phenobarbital decreased by 19.3% in patients with CYP2C19*1/*3 or the poor metabolizers of CYP2C19 compared with patients with normal CYP2C19 or with CYP2C19*1/*2. CONCLUSION: These findings indicated that the genetic polymorphisms of CYP2C19 contribute to the pharmacokinetic variability of phenytoin and phenobarbital, the poor metabolizers of CYP2C19, which are relatively common in Asian groups. |
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Authors:
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E Yukawa; K Mamiya |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of clinical pharmacy and therapeutics Volume: 31 ISSN: 0269-4727 ISO Abbreviation: J Clin Pharm Ther Publication Date: 2006 Jun |
Date Detail:
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Created Date: 2006-06-22 Completed Date: 2006-12-11 Revised Date: 2008-05-28 |
Medline Journal Info:
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Nlm Unique ID: 8704308 Medline TA: J Clin Pharm Ther Country: England |
Other Details:
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Languages: eng Pagination: 275-82 Citation Subset: IM |
Affiliation:
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Laboratory of Evidence-Based Pharmacotherapy, College of Pharmaceutical Sciences, Daiichi University, Minami-Ku, Fukuoka, Japan. yukawa@daiichi-cps.ac.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Algorithms Anticonvulsants / pharmacokinetics* Aryl Hydrocarbon Hydroxylases / genetics* DNA / genetics Female Gene Frequency Genotype Humans Japan / epidemiology Male Middle Aged Mixed Function Oxygenases / genetics* Models, Statistical Nonlinear Dynamics Phenobarbital / pharmacokinetics* Phenytoin / pharmacokinetics* Polymorphism, Genetic Population Reverse Transcriptase Polymerase Chain Reaction |
| Chemical | |
Reg. No./Substance:
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0/Anticonvulsants; 50-06-6/Phenobarbital; 57-41-0/Phenytoin; 9007-49-2/DNA; EC 1.-/Mixed Function Oxygenases; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/CYP2C19 protein, human |
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