Lack of effect of ondansetron on the pharmacokinetics and analgesic effects of morphine and metabolites after single-dose morphine administration in healthy volunteers

Br J Clin Pharmacol. 2001 Apr;51(4):309-16. doi: 10.1046/j.1365-2125.2001.01369.x.

Abstract

Aims: The purpose of this investigation was to study the influence of ondansetron on the single-dose pharmacokinetics and the analgesic effects elicited by morphine and the 3- and 6-glucuronide metabolites of morphine in healthy volunteers.

Methods: This was a randomized, double-blind, placebo-controlled, two-way crossover study in which six male and six female subjects were administered a single 10 mg intravenous dose of morphine sulphate, followed 30 min later by a single 16 mg intravenous dose of ondansetron hydrochloride or placebo. Serum and urine concentrations of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) samples were quantified over 48 h using high performance liquid chromatography with detection by mass spectrometry. Analgesia was assessed in the volunteers with a contact thermode device to provide a thermal pain stimulus. Four analgesic response variables were measured including thermal pain threshold, thermal pain tolerance, temporal summation of pain and mood state.

Results: The two treatments appeared to be equivalent based on the 90% confidence intervals (0.6, 1.67) of the least squares means ratio. All least squares means ratio confidence intervals for each parameter, for each analyte fell within the specified range, demonstrating a lack of an interaction.

Conclusions: The results of this study suggest that administration of ondansetron (16 mg i.v.) does not alter the pharmacokinetics of morphine and its 3- or 6-glucuronide metabolites to a clinically significant extent, nor does it affect the overall analgesic response to morphine as measured by the contact thermode system.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / pharmacokinetics*
  • Analgesics, Opioid / pharmacology*
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Interactions
  • Female
  • Humans
  • Male
  • Middle Aged
  • Morphine / administration & dosage
  • Morphine / pharmacokinetics*
  • Morphine / pharmacology*
  • Morphine Derivatives / pharmacokinetics
  • Morphine Derivatives / pharmacology
  • Ondansetron / adverse effects
  • Ondansetron / pharmacology*
  • Pain Measurement
  • Placebos
  • Serotonin Antagonists / adverse effects
  • Serotonin Antagonists / pharmacology*

Substances

  • Analgesics, Opioid
  • Morphine Derivatives
  • Placebos
  • Serotonin Antagonists
  • Ondansetron
  • morphine-6-glucuronide
  • Morphine
  • morphine-3-glucuronide