The analgesic activity of morphine-6-glucuronide

Br J Clin Pharmacol. 1992 Aug;34(2):130-8. doi: 10.1111/j.1365-2125.1992.tb04121.x.


1. The pharmacokinetics, cardio-respiratory effects and analgesic effects of intravenous morphine-6-glucuronide were studied in 20 cancer patients with pain. Four different dose levels (0.5, 1, 2, and 4 mg 70 kg-1) were studied. Plasma concentrations of morphine-6-glucuronide were measured for 12 h after dosing. Pulse rate, respiratory rate and blood pressure were monitored, and pain relief was measured using two rating scales and a visual analogue scale. 2. The mean elimination half-life (+/- s.d.) of morphine-6-glucuronide was 3.2 +/- 1.6 h. The mean AUC standardised to a dose of 1 mg 70 kg-1 was 390 +/- 263 nmol l-1 h. Mean morphine-6-glucuronide clearance was 96 +/- 38 ml min-1. There was a direct relationship between morphine-6-glucuronide plasma clearance and calculated creatinine clearance (r = 0.81, P less than 0.001). 38 +/- 22% of the dose of morphine-6-glucuronide was recovered unchanged in the urine in 24 h. No morphine or morphine-3-glucuronide was detected in the plasma or urine of any patient after morphine-6-glucuronide treatment. 3. Morphine-6-glucuronide exerted a useful analgesic effect in 17/19 assessable patients for periods ranging between 2 and 24 h. No correlation was observed between dose or plasma morphine-6-glucuronide concentrations, and duration or degree of analgesia. No clinically significant changes in cardio-respiratory parameters were observed. No patients reported sedation or euphoria. Nausea and vomiting were notably absent in all cases. 4. Morphine-6-glucuronide is an effective and well-tolerated analgesic. It is likely that the majority of the therapeutic benefit of morphine is mediated by morphine-6-glucuronide.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Adult
  • Aged
  • Analgesics / administration & dosage
  • Analgesics / pharmacokinetics
  • Analgesics / therapeutic use*
  • Blood Pressure / drug effects
  • Half-Life
  • Humans
  • Male
  • Middle Aged
  • Morphine Derivatives / adverse effects
  • Morphine Derivatives / pharmacokinetics
  • Morphine Derivatives / therapeutic use*
  • Neoplasms / complications
  • Pain Measurement
  • Pain, Intractable / drug therapy*
  • Pain, Intractable / etiology
  • Respiration / drug effects


  • Analgesics
  • Morphine Derivatives
  • morphine-6-glucuronide