Pharmacokinetics of Unchanged Morphine in Normal and Cirrhotic Subjects

Published reports of morphine pharmacokinetics differ, perhaps because of analytical discrepancies and different study protocols. A highly specific radioimmunoassay (N-carboxymethylnormorphine RIA) was used to measure unchanged morphine in plasma in six normal subjects and in eight cirrhotic patients with hypoalbuminemia, hyperbilirubinemia, and prolonged prothrombin time. All subjects received a single intravenous bolus of morphine hydrochloride (0.1 mg/kg). Peripheral blood samples were collected at frequent intervals from 2 min to 36 hr after injection. In cirrhotic patients as compared with normal subjects, terminal half-life of unchanged morphine was longer (201 +/- 39 vs 111 +/- 32 min (mean +/- SD), P less than 0.01) and total body clearance was slower (21 +/- 7.5 vs 33.5 +/- 8 ml X min-1 X kg-1, P less than 0.05). The apparent volume of distribution and the steady-state volume of distribution did not differ in the two groups. In conclusion, cirrhotic patients have a prolonged terminal half-life of unchanged morphine that is attributable to a decrease in total body clearance.