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Limited phase I study of morphine-3-glucuronide
R T Penson1, S P Joel, S Clark
1Division of Hematology/Oncology, Massachusetts General Hospital, 100 Blossom Street, Cox 640, Boston, Massachusetts 02114, USA. rpenson@partners.org
Journal of Pharmaceutical Sciences
|December 18, 2001
Summary
Morphine-3-glucuronide (M3G) showed minimal toxicity in healthy volunteers at tested doses. This study found no significant adverse effects or changes in vital signs, indicating M3G is well-tolerated.
Area of Science:
- Pharmacology
- Clinical Toxicology
Background:
- Morphine-3-glucuronide (M3G) is a major metabolite of morphine.
- Understanding M3G toxicity is crucial for pain management and opioid pharmacokinetics.
Purpose of the Study:
- To investigate the toxicity and pharmacokinetics of intravenous morphine-3-glucuronide (M3G) in healthy volunteers.
- To assess potential neuroexcitatory and opioid effects of M3G at single doses.
Main Methods:
- Open, uncontrolled, single-blinded, single-dose study.
- Three cohorts of healthy volunteers (n=3 per cohort) received 7.5, 15, or 30 mg/70 kg IV M3G.
- Plasma M3G concentrations measured via HPLC; subjective toxicity and vital signs recorded over 24 hours.
Main Results:
- No significant changes in cardiovascular or respiratory parameters were observed.
- Subjective toxicity assessments revealed virtually no adverse effects.
- Pharmacokinetics followed a two-compartment model with a mean elimination half-life of 1.66 hours.
Conclusions:
- M3G demonstrated a favorable safety profile at the investigated doses.
- No clear neuroexcitatory or opioid effects were detected.
- M3G pharmacokinetics were comparable to those of morphine-6-glucuronide (M6G).