Presystemic metabolism of meperidine to normeperidine in normal and cirrhotic subjects

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Abstract
Plasma concentrations and urinary excretion of meperidine and its metabolite, normeperidine, were determined after i.v. and oral administration to 11 men; 5 men had hepatic cirrhosis and 6 were normal. Systemic clearance of meperidine was smaller and bioavailability and half-life were greater in the cirrhotic patients than in the normal subjects. Plasma concentrations and 24 h urinary excretion of normeperidine was lower and the persistence of normeperidine in plasma was longer in the patients with cirrhosis. The route of administration did not alter the fraction of normeperidine generated from meperidine. In patients requiring repeated meperidine dosage, the drug should be taken parenterally rather than orally to allow maximal analgesia and minimal formation of normeperidine. Patients with cirrhosis may be relatively protected from normeperidine toxicity due to impaired formation, but the risk of cumulative toxicity may be greater than in normal subjects due to slower elimination of the metabolite and greater sensitivity to the effects of narcotics on the CNS.