Limited phase I study of morphine-3-glucuronide

✍ Scribed by Richard T. Penson; Simon P. Joel; Simon Clark; Anna Gloyne; Maurice L. Slevin

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 171 KB
• Volume: 90
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.1131

✦ Synopsis

The toxicity of morphine-3-glucuronide (M3G) has been investigated in an open, uncontrolled, single-blinded, single dose study over a limited range of doses. Three cohorts each of three healthy volunteers received 7.5, 15, and 30 mg/70 kg intravenous (IV) M3G. Blood sampling was undertaken for the following 24 h. Subjective toxicity was recorded on visual analogue scales and plasma M3G concentrations measured by a speci®c HPLC assay. Virtually no effects and no change in cardiovascular or respiratory parameters were seen. The pharmacokinetics ®tted a two-compartment model. The mean elimination half-life (AE S.D.) of M3G was 1.66 (AE 0.47) h. Mean AUC standardized to a dose of 1 mg/70 kg was 228 (AE 62) hmolL À1 Á h. Mean M3G clearance was 169 (AE 48) mLmin À1 and the mean volume of distribution was 23.1 (AE 4.8) liters. At the doses investigated there were no clear neuroexcitatory effects, no opioid effects, and the pharmacokinetics were very similar to those of morphine-6-glucuronide (M6G).