title: Lack of effect of ondansetron on the pharmacokinetics and analgesic effects of morphine and metabolites after single-dose morphine administration in healthy volunteers.
abstract: OBJECTIVE
  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.
authors.affiliation: GlaxoSmithKline Inc., Research Triangle Park, NC, USA,
authors.forename: K R
authors.initials: KR
authors.lastname: Crews
authors.forename: B P
authors.initials: BP
authors.lastname: Murthy
authors.forename: E K
authors.initials: EK
authors.lastname: Hussey
authors.forename: A N
authors.initials: AN
authors.lastname: Passannante
authors.forename: J L
authors.initials: JL
authors.lastname: Palmer
authors.forename: W
authors.initials: W
authors.lastname: Maixner
authors.forename: K L
authors.initials: KL
authors.lastname: Brouwer
mesh_terms: D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D009022:Morphine Derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D017294:Ondansetron / Q000009:adverse effects / Q000494:pharmacology*; D010147:Pain Measurement; D010919:Placebos; D012702:Serotonin Antagonists / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D000701:Analgesics, Opioid; D009022:Morphine Derivatives; D010919:Placebos; D012702:Serotonin Antagonists; D017294:Ondansetron; C035349:morphine-6-glucuronide; D009020:Morphine; C018108:morphine-3-glucuronide