Review of the pharmacokinetics, pharmacogenetics, and drug interaction potential of antidepressants: Focus on venlafaxine

Improving outcomes for patients with depression involves selecting the best possible drug,rr therapy. Considerations relevant to drug product selection include: I) pharmacokinetic issues such as half-life and ti time to steady-state, and protein binding; 2) pharmacodynamic drug-drug interactions; and 3) drag metabolism-related drug interactions. A comparison of selected anti-depressants with an emphasis on venlafaxine's similarities and differences is presented. Based on these parameters, selecting an antidepressant medication, such as venlafaxine, that has a low, potential for drug interactions at the Cytochrome P450 (CYP) enzyme system, and is easy to monitor and dose, facilitate successful treatment of patients. Venlafaxine has been evaluated in clinical studies that demonstrate low to negligible drag interaction potential at CI CYP2D6, CYP1A2, CYP2C19, and CYP3A4. Its short half-life and time to steady-state, when coupled with the extended release characteristics of the preferred dosage formulation allow for once daily dosing and rapid attainment of therapeutic effects. The CYP3A4 system is involved kt both first-pass metabolism and systemic clearance of medications. Drug interactions at this isoenzyme have prover? to be of high clinical relevance ranging from cardiovascular toxicity and death with commonly used drugs such as cisapride, to subtherapeutic levels of cyclosporine or protease inhibitors lead to transplant rejection or HIV relapse. Reasons for the under detection and reporting of drug interaction mediated adverse events include healthcare system structure, the poor return to follow up of non-adherent patients, the need for greater education and training of clinicians to recognize drug-related adverse events, and the reluctance of patients to spontaneously communicate about the unpleasant effects of their medication. (C) 2000 Wiley-Liss, Inc.