Presystemic metabolism of meperidine to normeperidine in normal and cirrhotic subjects.
Plasma concentrations and urinary excretion of meperidine and its metabolite normeperidine were determined after intravenous and oral administration to 11 men; five men had hepatic cirrhosis and six were normal. Systemic clearance of meperidine was smaller and bioavailability and half-life greater in the cirrhotic patients than in the normal subjects. Plasma concentrations and 24-hr urinary excretion of normeperidine was lower and persistence of normeperidine in plasma longer in the patients with cirrhosis. The route of administration did not alter the fraction of normeperidine generated from meperidine. The results suggest that 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 because of impaired formation, but the risk of cumulative toxicity may be greater than in normal subjects because of slower elimination of the metabolite and greater sensitivity to the effects of narcotics on the central nervous system.[1]References
- Presystemic metabolism of meperidine to normeperidine in normal and cirrhotic subjects. Pond, S.M., Tong, T., Benowitz, N.L., Jacob, P., Rigod, J. Clin. Pharmacol. Ther. (1981) [Pubmed]
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