ABSENCE OF EFFECT OF SERTRALINE ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF PHENYTOIN

A double-blind, randomized, placebo-controlled study assessed the effe cts of sertraline on the pharmacokinetics and pharmacodynamics of phen ytoin in 30 healthy male volunteers. Method: All subjects received phe nytoin throughout the study. The dose of phenytoin was 100 mg three ti mes daily; steady-state trough plasma phenytoin concentrations were de termined on Day 6. Concurrent treatment with sertraline (16 subjects) or placebo (13 subjects) was initiated on Day 8 and continued througho ut the study in those subjects whose trough plasma phenytoin concentra tions were between 5 and 20 mu g/mL. The dose of sertraline was increa sed from 50 to 200 mg/day over 7 days; the 200-mg dose was then admini stered for 10 days. The plasma phenytoin concentration-time profile wa s determined on Day 7 before the start of sertraline or placebo dosing and at the end of dosing on Day 24. Psychometric testing was done bef ore and after dosing on Days 0, 7, and 24. Results: There were no sign ificant differences between the sertraline group and the placebo group in the pharmacokinetic parameters of phenytoin. In addition, there wa s no indication that administration of phenytoin alone or concomitant administration of phenytoin and sertraline impaired cognitive function . Treatment-related side effects, primarily headache and nausea, were reported in 8 of 16 sertraline subjects and in 5 of 13 placebo subject s. Two subjects in the sertraline group withdrew because of side effec ts (rash), and 3 subjects in the placebo group withdrew because of sid e effects (rash and headache). Conclusion: High dosages of sertraline did not affect the pharmacokinetics or the pharmacodynamics of phenyto in in this study performed in healthy volunteers.