PHARMACOKINETICS OF TRAPIDIL IN PATIENTS WITH CHRONIC LIVER-DISEASE

The pharmacokinetics of trapidil were studied in 15 patients with chro nic liver disease (12 with hepatic cirrhosis, 2 with alcoholic fatty l iver, 1 with liver fibrosis). Trapidil was administered intravenously as a 100-mg bolus. Serum samples were analyzed for trapidil by means o f high-performance liquid chromatography, Mean pharmacokinetic paramet ers were compared with those found in a previous study of 12 healthy v olunteers, Total plasma clearance was decreased significantly in patie nts with hepatic cirrhosis (96 mL/min versus 258 mL/min in healthy ind ividuals and 252 mL/min in patients with noncirrhotic liver disease). No difference in clearance was observed between patients with compensa ted or decompensated cirrhosis, and portal hypertension did not affect this clearance of trapidil. It can be concluded that trapidil clearan ce is a parameter that is very sensitive to alterations in hepatic cle arance caused by liver cirrhosis, and that the dosage of trapidil shou ld be adjusted accordingly in such patients.