[Prolonged intravenous infusion of morphine. Pharmacokinetic study]

Critically ill patients require optimal pain control without undesirable side-effects. Continuous intravenous morphine infusion is often chosen instead of the conventional intermittent administration. In the present study, the pharmacokinetic characteristics of morphine were studied in five subjects receiving a constant rate intravenous infusion with the attainment of a steady state. The plasma levels were compared with values derived from bolus intravenous administration in five other patients. The concentrations of unchanged morphine were determined in serum using high performance liquid chromatography with an electrochemical detector. The decay of plasma concentrations after a single dose fitted a triexponential function consistent with a three compartment pharmacokinetic model. Postinfusion plasma concentrations fitted a two compartment model. Derived values (mean +/- SEM) of total body clearance were significantly different between groups (p less than 0.05), while mean values of terminal elimination half-life (t 1/2 Kel) were similar. It was concluded that values of total distribution volume were significantly different. The extent of morphine distribution varied more than twofold between the two groups of patients. This was interpreted as a consequence of an important underestimation in the extent of distribution tissues after administration of a single dose.