The analgesic activity of morphine-6-glucuronide.
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)
Osborne
R
R
Imperial Cancer Research Fund Department of Medical Oncology, St Bartholomew's Hospital, London.
Thompson
P
P
Joel
S
S
Trew
D
D
Patel
N
N
Slevin
M
M
D000328:Adult; D000368:Aged; D000700:Analgesics / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009022:Morphine Derivatives / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009369:Neoplasms / Q000150:complications; D010147:Pain Measurement; D010148:Intractable Pain / Q000188:drug therapy* / Q000209:etiology; D012119:Respiration / Q000187:drug effects
D000700:Analgesics; D009022:Morphine Derivatives; C035349:morphine-6-glucuronide