Evaluation of the influence of sex and CYP2C19 and CYP2D6 polymorphisms in the disposition of citalopram
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- 作者：Salvador Fudio ; Alberto M. Borobia ; Enrique Piñ ; ana ; Elena Ramí ; rez ; Beatriz Tabaré ; s ; Pedro Guerra ; Antonio Carcas ; Jesú ; s Frí ; as
- 关键词：CYP2C19 polymorphism ; CYP2D6 polymorphism ; Gender ; Citalopram
- 刊名：European Journal of Pharmacology
- 出版年：2010
- 出版时间：25 January 2010
- 年：2010
- 卷：626
- 期：2-3
- 页码：200-204
- 全文大小：194 K
文摘
We investigate the impact of sex and genotype on citalopram disposition in 35 healthy volunteers who received an oral dose of 20 mg citalopram within a single-dose bioequivalence study. CYP2C192 and 3, and CYP2D64 mutations were determined by Real-Time PCR. The influence of sex and genotype was analyzed by a linear mixed model for repeated measures, including formulation, period, sequence, sex, CYP2C19 and CYP2D6 as fixed effects and subject nested sequencesexCYP2C19CYP2D6 as the random one. Pharmacokinetic parameters were log-transformed and AUC∞ and Cmax adjusted to the administered dose/weight. The model yields a statistical significance in AUC∞ and CL/F for CYP2C19 and CYP2D6. Gender, formulation, sequence or period effects were not statistically significant. AUC∞ of CYP2C191/2 and CYP2C192/2 carriers is 44 % and 118 % higher than wild type, respectively; CYP2D6 volunteers carrying 1/4 have an AUC 23 % higher than wild type. Our data also suggest that the influence of CYP2D6 on AUC∞ is very low when it is in association with CYP2C191/1 while its influence is more apparent in association with CYP2C191/2. In conclusion, we demonstrate the influence of CYP2C19 and CYP2D6 in the disposition of citalopram, and we suggest that the influence of CYP2D6 is more probable in volunteers with at least one defective allele of CYP2C19.