The analgesic activity of morphine-6-glucuronide.

Abstract

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)

• Authors: R Osborne, P Thompson, S Joel, D Trew, N Patel, M Slevin
• Journal: British journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 34 Issue 2 Pg. 130-8 (Aug 1992) ISSN: 0306-5251 [Print] England
• PMID: 1419474 (Publication Type: Journal Article)

Chemical References

• Analgesics
• Morphine Derivatives
• morphine-6-glucuronide

Topics

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