Disposition of morphine-6-glucuronide and morphine in healthy volunteers

The pharmacokinetics and subjective side effects of i.v. morphine sulphate 120 micrograms kg-1 and morphine-6-glucuronide (M6G) 30 micrograms kg-1 were determined in six healthy volunteers, using a placebo-controlled, single-blind randomized crossover design. Five of these volunteers underwent an additional (non-randomized) study of M6G 60 micrograms kg-1. Subjective side effects were similar following both drugs, but of shorter duration following M6G. Morphine was not detected after administration of M6G. For M6G 30 micrograms kg-1 the mean (SD) volume of distribution, elimination half-life and clearance were 29.38 (18.36) litre, 2.05 (1.2) h and 187.81 (37.41) litre h-1, respectively. These values were not significantly different from those obtained for M6G 60 micrograms kg-1. In all subjects the volumes of distribution and clearances were significantly smaller for M6G than for morphine, but the elimination half-lives were similar.