MINIMAL BILIARY-EXCRETION AND ENTEROHEPATIC RECIRCULATION OF METOCLOPRAMIDE IN PATIENTS WITH EXTRAHEPATIC CHOLESTASIS

The biliary excretion and apparent oral clearance of metoclopramide (M CL) were determined after oral administration of 1 mg MCL/kg body weig ht to 10 patients suffering from extrahepatic cholestasis with nasobil iary tube for drainage of the common bile duct. A bilioduodenal endopr osthesis was subsequently fitted in 6 of these patients, i. e. the ent erohepatic circulation was restored, and the apparent oral clearance w as re-determined. Biliary excretion, comprising free MCL and the produ cts of conjugation, accounted for less than 1% of the administered dos e. In accordance with this, the median areas under the plasma concentr ation-time-curves AUC(0-15 h) in patients with intact and interrupted enterohepatic recirculation were of similar size. The pharmacokinetic values in patients with cholestasis (median apparent oral clearance 0. 5 1. kg-1 . h-1; median t1/2 4.5 h) were similar to those previously r eported in patients with healthy liver function. We conclude that it i s not necessary to adjust single doses of MCL in patients recovering f rom obstructive jaundice.