Cholestasis and hepatic drug metabolism. Comparison of metabolic clearance rate of antipyrine in patients with intrahepatic or extrahepatic cholestasis.

The antipyrine metabolic clearance rate (MCR) was studied in two groups of patients with similar degrees of cholestasis and hepatic damage, but differing mechanisms of cholestasis. The plasma disappearance rate of antipyrine in 18 patients with extrahepatic cholestasis and 11 patients with intrahepatic cholestasis was compared with that of two groups of control subjects without liver disease who were matched for age. Whereas no significant difference was observed for the antipyrine MCR between patients with extrahepatic cholestasis and their controls [30.7 +/- 11.2 (SD) as against 31.6 +/- 10.0 ml/min], the antipyrine MCR was significantly lower (P less than 0.001) in the patients with intrahepatic cholestasis than in their controls (16.2 +/- 4.5 vs 37.4 +/- 17.3 ml/min). These results suggest that cholestasis per se does not change the rate of metabolism of drugs by the liver. The decrease of antipyrine MCR in patients with intrahepatic cholestasis could be due to a reduced functional parenchymal mass related to some degree of hepatic necrosis.