Translational pharmacokinetics: current issues with newer antidepressants

Area of Science:

• Pharmacology
• Clinical Pharmacy
• Drug Metabolism

Background:

• Translational pharmacokinetics bridges drug metabolism and disposition knowledge with clinical practice.
• Newer antidepressants exhibit diverse pharmacokinetic profiles and potential for drug interactions.
• Clinical questions drive laboratory investigations, with findings informing patient care.

Purpose of the Study:

• To highlight unresolved issues in the clinical application of newer antidepressant pharmacokinetics.
• To emphasize the importance of understanding drug interactions and disposition for effective prescribing.
• To underscore the need for established therapeutic plasma concentration ranges for optimizing drug dosing.

Main Methods:

• Review of pharmacokinetic properties of newer antidepressant medications.
• Analysis of drug metabolism pathways, including active metabolites and stereochemistry.
• Examination of cytochrome P-450 isozyme interactions and potential for drug-drug interactions.

Main Results:

• Significant variability exists in the pharmacokinetic properties and cytochrome P-450 interactions among newer antidepressants, including selective serotonin reuptake inhibitors (SSRIs).
• Clinical significance of stereochemistry, active metabolites, and nonlinear disposition remains poorly understood.
• Lack of established therapeutic plasma concentration ranges complicates dosing for nonresponsive patients.

Conclusions:

• Translating pharmacokinetic knowledge of newer antidepressants into clinical practice is crucial for effective drug dosage regimens.
• Careful consideration of drug interactions is necessary when prescribing combinations of these agents.
• Further research is needed to address unresolved pharmacokinetic and clinical dosing issues.