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The effect of ritonavir on the pharmacokinetics of meperidine and normeperidine
S C Piscitelli1, D R Kress, R J Bertz
1Pharmacy Department, Clinical Center and Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Study Objective:
To determine the effects of ritonavir on the pharmacokinetics 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 immunodeficiency virus.
Intervention:
Subjects received oral meperidine 50 mg and had serial blood samples collected for 48 hours. They then received ritonavir 500 mg twice/day for 10 days, followed by administration of a second 50-mg meperidine dose 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) decreased 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 induction of hepatic metabolism.
Conclusion:
Meperidine's AUC is significantly reduced, not increased, by concomitant ritonavir. Based on these findings, the risk of narcotic-related adverse effects from this combination appears to be minimal. However, increased concentrations of normeperidine suggest a potential for toxicity with increased dosages or long-term therapy.