Pharmacokinetics of morphine and its glucuronides after intravenous infusion of morphine and morphine-6-glucuronide in healthy volunteers*

Abstract

Steady‐state pharmacokinetics of morphine and morphine‐6‐glucuronide (M‐6‐G) after intravenous administration of either morphine or M‐6‐G were determined in healthy volunteers. With a dosing regimen calculated on the basis of data obtained in a first series of experiments in four subjects (morphine: intravenous loading dose of 0.24 mg/kg for 5 minutes and an intravenous infusion of 0.069 mg · kg⁻¹ · hr⁻¹ for 4 hours; M‐6‐G: loading dose of 0.011 mg/kg for 5 minutes and an infusion of 0.006 mg · kg⁻¹ · hr⁻¹ for 4 hours), it was possible to yield plasma concentrations of morphine and M‐6‐G in another four subjects close to predefined targeted levels (35 and 45.5 ng/ml morphine and M‐6‐G, respectively). This dosing regimen may be used in further pharmacodynamic studies to compare the analgesic effects of morphine and M‐6‐G. In addition, metabolite kinetics of M‐6‐G were calculated as a function of time with use of a linear systems approach to the estimation of rate and fraction of morphine glucuronidation to M‐6‐G. Clinical Pharmacology & Therapeutics (1996) 60, 316–325; doi: