CYP2C19 polymorphism is not important for the in vivo metabolism of selegiline

被引:14
作者
Laine, K
Anttila, M
Nyman, L
Wahlberg, A
Bertilsson, L
机构
[1] Univ Turku, Dept Pharmacol & Clin Pharmacol, FIN-20520 Turku, Finland
[2] Huddinge Univ Hosp, Karolinska Inst, Div Clin Pharmacol, Dept Med Lab Sci & Technol, S-14186 Huddinge, Sweden
[3] Orion Corp Farmos, Orion Pharma, FIN-20101 Turku, Finland
关键词
selegiline; CYP2C19; phenotype;
D O I
10.1007/s002280100289
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Objectives: To address the relevance of cytochrome P-450 (CYP) 2C19 polymorphism for the pharmacokinetics and dynamics of selegiline and its two known primary metabolites, desmethylselegiline and 1-methamphetamine. Methods: Six extensive (mephenytoin S/R ratio <0.3; EM) and six poor (mephenytoin S/R ratio >0.8; PM) hydroxylators of S-mephenytoin ingested a single 10-mg oral dose of selegiline hydrochloride. Serum concentrations of selegiline, desmethylselegiline and l-methamphetamine were measured by gas chromatography mass spectrometry for up to 48 h. In addition, the platelet monoamine oxidase type B (MAO-B) activity was measured for 14 days to describe possible differences in the pharmacodynamics of selegiline and its metabolites between EM and PM. Results: The CYP2C19 phenotype had no significant effects on the pharmacokinetic variables of selegiline. PM of S-mephenytoin had 68% higher mean AUC of desmethylselegiline (P=0.0017) than EM, but no significant differences were observed in other pharmacokinetic parameters of desmethylselegiline. Contrary to desmethylselegiline, the serum 1-methamphetamine concentrations were slightly lower in PM, but no statistically significant differences were observed in l-methamphetamine pharmacokinetics between the two CYP2C19 phenotypes. Accordingly, the magnitude of MAO-B inhibition showed no significant differences between the study groups. Conclusions: CYP2C19 polymorphism does not seem to be crucial for the metabolism or clinical effects of selegiline.
引用
收藏
页码:137 / 142
页数:6
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