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Effect of CYP2C19 genetic polymorphism on pharmacokinetics of phenytoin and phenobarbital in Japanese epileptic patients using Non‐linear Mixed Effects Model approach
Author(s) -
Yukawa E.,
Mamiya K.
Publication year - 2006
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/j.1365-2710.2006.00712.x
Subject(s) - cyp2c19 , phenytoin , pharmacokinetics , phenobarbital , pharmacology , medicine , epilepsy , metabolism , cytochrome p450 , psychiatry
Summary 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.