¹Department of Experimental and Clinical Pharmacology and Toxicology and the Department of Pharmaceutical Chemistry, University of Erlangen-Nürnberg, Erlangen, Germany

Correspondence: Jörn Lötsch, MD, Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Universitätsstrasse 22, D-91054 Erlangen, Germany.

^*Supported by grants from the Bundesinstitut für Arzneimittel und Medizinprodukte, Berlin, Germany (Fo 2.1-1326-109), and the German Ministry of Science and Technology, Bonn, Germany (01EC9403).

Received 6 December 1995; Accepted 16 May 1996.

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.