Translational pharmacokinetics: current issues with newer antidepressants

Translational pharmacokinetics involves the application of our knowledge of drug metabolism and disposition to clinical practice. The newer antidepressants are a diverse group of compounds in terms of pharmacokinetic properties and the potential for participation in drug interactions. Clinical questions have been taken into the laboratory and the results back into the clinic. Unfortunately, several issues are unresolved. The clinical significance of the stereochemistry of the newer antidepressants is poorly investigated. Several drugs produce pharmacologically active metabolites and demonstrate nonlinearity in their disposition. Plasma concentration ranges associated with therapeutic benefits have not been established to guide drug dosing in nonresponsive patients. Each of the newer antidepressants has a distinct profile of affinity for cytochrome P-450 isozymes. Even within the class of selective serotonin reuptake inhibitors (SSRIs), inhibition of P-450 isozymes differ substantially. Care must be taken when prescribing certain drug combinations to control drug interactions. Translating the pharmacokinetic differences among the newer antidepressants to clinical practice has significance for designing effective drug dosage regimens.