Clin Pharmacokinet
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Review Meta Analysis
Impact of cytochrome P450 2C19 polymorphisms on citalopram/escitalopram exposure: a systematic review and meta-analysis.
Citalopram and escitalopram, selective serotonin reuptake inhibitors, are primarily metabolized by cytochrome P450 (CYP) 2C19, which is a highly polymorphic enzyme known to cause inter-individual differences in pharmacokinetics. However, the impact of CYP2C19 polymorphisms on citalopram or escitalopram exposure has yet to be fully clarified, especially with regard to the quantitative impact of the CYP2C19*17 allele. ⋯ This is the first meta-analysis based on a systematic review of accumulated information that addresses the relationship between CYP2C19 genotypes and the exposure to citalopram or escitalopram. All functional CYP2C19 genotype groups demonstrated significant effects on (es)citalopram exposure. The findings based on our pooled analysis are likely to help in understanding the inter-individual variability in the exposure to citalopram and escitalopram in psychiatric patients and to facilitate dose selection, particularly for the homozygous carriers of CYP2C19*2 or *3 (loss of function) and CYP2C19*17 (gain of function) alleles. The results could improve individualization of citalopram or escitalopram therapy and could also be used for physiologically based pharmacokinetic modeling as well as pharmacokinetic/pharmacodynamic modeling.