PHARMACOKINETICS OF SINGLE-DOSE I.V.MORPHINE IN NORMAL VOLUNTEERS AND PATIENTS WITH END-STAGE RENAL FAILURE

Morphine 0.125 mgkg^–1 was administered i.v. to 11 normalsubjects and nine patients with chronic renal failure requiringregular haemodialysis. Plasma morphine concentrations were measuredusing high pressure liquid chromatography (HPLC). Although therewas considerable individual variation in both groups, mean plasmaconcentrations of morphine were significantly higher in thepatients with renal failure for 15 min after administration.The decay of plasma concentration fitted a three-compartmentmamillary pharmacokinetic model in all subjects. Derived values(mean $ SEM) of T^x, volume of distribution of the second compartment(V₂), total volume of distribution at steady state ( V^ss1) andtransfer rate constant from the first to the second compartment(k₁₂) were significantly different between groups. Mean valuesof terminal elimination half-life (T⁷) and total body clearancewere similar in the two groups. It was concluded that eliminationof unchanged morphine is not impaired significantly in patientswith chronic renal failure, although accumulation of morphine-3-glucuronideprobably occurs. Although the pharmacological effect of morphineis not related temporally to plasma morphine concentrations,the higher values in patients with renal failure may be implicatedin their increased sensitivity to the drug