| Abstract: | The pharmacokinetics of trapidil (Rocornal, Deutsches Hydrierwerk Rodleben GmbH) were studied in 15 patients with chronic liver disease (12 patients with hepatic cirrhosis, 2 patients with alcoholic fatty liver, one patient with liver fibrosis). Trapidil was given orally (200 mg, Rocornal dragees 100 mg) as well as intravenously (100 mg) in random order. Serum samples were analyzed for trapidil by HPLC. The pharmacokinetic parameters were compared with the parameters of 12 healthy volunteers, investigated by Weiss [1991]. Total plasma clearance was decreased significantly in patients with hepatic cirrhosis (99.6 ml/min vs 273.1 ml/min in controls and 255.3 ml/min in patients with non cirrhotic liver disease). However, there was no difference in clearance between patients with compensated and patients with decompensated cirrhosis. Clearance and aspartate aminotransferase activity correlated inversely. In addition, in some of the patients suffering from portal hypertension delayed absorption was observed, but the difference did not reach statistical significance. The volumes of distribution were significantly lower in patients with non alcoholic cirrhosis (19.9 l vs 36.8 l in controls and 41.0 l in patients with alcoholic cirrhosis). It might be concluded from this study, that dosage adjustments are necessary in treatment of patients with cirrhosis. In patients suffering from portal hypertension an intravenous administration should be prefered. |
