The effect of ritonavir on the pharmacokinetics of meperidine and normeperidine

Study Objective. To determine the effects of ritonavir on the pharmacokinet ics of meperidine and normeperidine. Design. Open-label, crossover, pharmacokinetic study. Setting. United States government research hospital. Subjects. Eight healthy volunteers who tested negative for the human immuno deficiency virus. Intervention. Subjects received oral meperidine 50 mg and had serial blood samples collected for 48 hours. They then received ritonavir 500 mg twice/d ay for 10 days, followed by administration of a second 50-mg meperidine dos e and collection of serial samples. Measurements and Main Results. Plasma samples were assayed for meperidine, normeperidine, and ritonavir. Meperidine's area under the curve (AUC) decre ased in all subjects by a mean of 67 +/- 4% in the presence of ritonavir (p <0.005). Mean +/- SD maximum concentration was decreased from 126 +/- 47 to 51 +/- 21 ng/ml. Normeperidine's mean AUC was increased 47%, suggesting in duction of hepatic metabolism. Conclusion. Meperidine's AUC is significantly reduced, not increased, by co ncomitant ritonavir. Based on these findings, the risk of narcotic-related adverse effects from this combination appears to be minimal. However, incre ased concentrations of normeperidine suggest a potential for toxicity with increased dosages or long-term therapy.