Morphine Pharmacokinetics in Renal Failure
The effect of chronic renal failure (RF) on the pharmacokinetics of morphine was studied in nine patients with end-stage RF, aged 58 ± 8 yr (SD), and in seven control patients, aged 58 ± 15 yr, undergoing peripheral surgery under general anesthesia. All patients received 0.2 mg.kg−1 as an intravenous bolus injection. Blood samples were collected over a 36 h period, and plasma concentrations were measured using a specific radioimmunoassay method. Unchanged morphine could be identified for only 12 h in all patients. The mean plasma concentrations of unchanged morphine were similar in the two groups, except in the first sample (5 min) where it was higher (P < 0.05) in RF group. Patients with RF had a significantly smaller (P < 0.05) central compartment (0.3 ± 0.2 1.kg−1versus 0.8 ± 0.41.kg−1) than in the controls. Volume of distribution at steady state was also significantly (P < 0.05) decreased in RF patients (2.8 ± 1.0 1.kg−1) versus 3.7 ± 1.2 1.kg−1 in the normal patients. The total apparent volume of distribution, the elimination half-life, and the plasma clearance were similar in the two groups. Identical peak levels of morphine metabolites were observed in the two groups, but plasma concentration of morphine metabolites was undetectable after 12 h in the control group and remained at a high level of 82 ± 49 ng.ml−1 at 24 h and 83 ± 57 ng.ml−1 at 36 h in RF patients. In conclusion, RF did not alter elimination of unchanged morphine, but induced an accumulation of morphine metabolites over 36 h at least, a fact which could explain the prolonged effect of the drug observed in patients with RF.