Minimal biliary excretion and enterohepatic recirculation of metoclopramide in patients with extrahepatic cholestasis

Summary The biliary excretion and apparent oral clearance of metoclopramide (MCL) were determined after oral administration of 1 mg MCL/kg body weight to 10 patients suffering from extrahepatic cholestasis with nasobiliary tube for drainage of the common bile duct. A bilioduodenal endoprosthesis was subsequently fitted in 6 of these patients, i.e. the enterohepatic circulation was restored, and the apparent oral clearance was re-determined.Biliary excretion, comprising free MCL and the products of conjugation, accounted for less than 1% of the administered dose. In accordance with this, the median areas under the plasma concentration-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 l·kg^–1·h^–1; median t_1/2 4.5 h) were similar to those previously reported in patients with healthy liver function.We conclude that it is not necessary to adjust single doses of MCL in patients recovering from obstructive jaundice.