Pharmacokinetics of single-dose i.v. morphine in normal volunteers and patients with end-stage renal failure

Abstract

Morphine 0.125 mg kg-1 was administered i.v. to 11 normal subjects and nine patients with chronic renal failure requiring regular haemodialysis. Plasma morphine concentrations were measured using high pressure liquid chromatography (HPLC). Although there was considerable individual variation in both groups, mean plasma concentrations of morphine were significantly higher in the patients with renal failure for 15 min after administration. The decay of plasma concentration fitted a three-compartment mamillary pharmacokinetic model in all subjects. Derived values (mean +/- SEM) of T 1/2 alpha, volume of distribution of the second compartment (V2), total volume of distribution at steady state (Vss) and transfer rate constant from the first to the second compartment (k12), were significantly different between groups. Mean values of terminal elimination half-life (T 1/2 gamma) and total body clearance were similar in the two groups. It was concluded that elimination of unchanged morphine is not impaired significantly in patients with chronic renal failure, although accumulation of morphine-3-glucuronide probably occurs. Although the pharmacological effect of morphine is not related temporally to plasma morphine concentrations, the higher values in patients with renal failure may be implicated in their increased sensitivity to the drug.