@entity5320 inhibition by selective @entity750 reuptake inhibitors: analysis of achievable steady-state plasma concentrations and the effect of ultrarapid metabolism at XXXX .

@entity1 @entity905 @entity5320 @entity14031 @entity903 @entity3755 @entity3756 @entity750 @entity3982
STUDY OBJECTIVE: To assess the correlation between plasma concentrations of four commonly administered selective @entity750 reuptake inhibitors (SSRIs) and the magnitude of cytochrome P450 (CYP) 2D6 inhibition. DESIGN: Prospective analysis. SETTING: University-affiliated research laboratory. @entity1 : Thirty-two healthy, drug-free volunteers. INTERVENTION: Subjects were randomized to four groups and received daily administration of either @entity905 60 mg (as a loading dose), @entity3755 100 mg, @entity903 20 mg, or @entity3756 100 mg for 8 days. MEASUREMENTS AND MAIN RESULTS: The urinary concentration ratio of @entity14031 : @entity3982 (interpreted as an in vivo index of @entity5320 activity) was determined for each subject before and after the 8 days of receiving SSRIs. Plasma SSRI trough concentrations were measured on days 6-9. The @entity5320 genotype was determined in a subject with an undetectable @entity903 concentration. Inhibition of @entity5320 correlated significantly with plasma concentrations of @entity903 and @entity905 . In contrast, no significant correlations emerged between @entity5320 inhibition and plasma concentrations of @entity3756 or @entity3755 . The subject with an undetectable @entity903 concentration was found to carry at least three functional @entity5320 genes. CONCLUSIONS: For @entity903 and @entity905 , plasma concentrations and dosage strongly influence the magnitude of enzyme inhibition. The potential of @entity903 (a @entity5320 substrate) as an inhibitor may be affected by the genotypes and metabolic capacities of individual subjects.
