Limited phase I study of morphine-3-glucuronide.
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 specific HPLC assay. Virtually no effects and no change in cardiovascular or respiratory parameters were seen. The pharmacokinetics fitted a two-compartment model. The mean elimination half-life (+/- S.D.) of M3G was 1.66 (+/- 0.47) h. Mean AUC standardized to a dose of 1 mg/70 kg was 228 (+/- 62) etamolL(-1) x h. Mean M3G clearance was 169 (+/- 48) mLmin(-1) and the mean volume of distribution was 23.1 (+/- 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).
Penson
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Division of Hematology/Oncology, Massachusetts General Hospital, 100 Blossom Street, Cox 640, Boston, Massachusetts 02114, USA. rpenson@partners.org
Joel
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SP
Clark
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S
Gloyne
A
A
Slevin
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ML
D000328:Adult; D000818:Animals; D019540:Area Under Curve; D000697:Central Nervous System Stimulants / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D009022:Morphine Derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D016037:Single-Blind Method
D000697:Central Nervous System Stimulants; D009022:Morphine Derivatives; C018108:morphine-3-glucuronide