The effect of ritonavir on the pharmacokinetics of meperidine and normeperidine.
OBJECTIVE
To determine the effects of ritonavir on the pharmacokinetics of meperidine and normeperidine.


METHODS
Open-label, crossover, pharmacokinetic study.


METHODS
United States government research hospital.


METHODS
Eight healthy volunteers who tested negative for the human immunodeficiency virus.


METHODS
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.


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.


CONCLUSIONS
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.
Piscitelli
S C
SC
Pharmacy Department, Clinical Center and Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Kress
D R
DR
Bertz
R J
RJ
Pau
A
A
Davey
R
R
D000328:Adult; D000701:Analgesics, Opioid / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002800:Cholinesterase Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D016001:Confidence Intervals; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D017320:HIV Protease Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008614:Meperidine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000097:blood / Q000493:pharmacokinetics*
D000701:Analgesics, Opioid; D002800:Cholinesterase Inhibitors; D017320:HIV Protease Inhibitors; D008614:Meperidine; C002752:normeperidine; D019438:Ritonavir