抄録
The pharmacokinetics of diltiazem (DTZ) was investigated in 7 control patients with normal liver function and 7 patients with liver cirrhosis. After chronic oral adminis tration of DTZ, 30 or 60 mg t. i. d., serum levels of DTZ and its active metabolites, deacetyl DTZ (DAD) and N-demethyl DTZ (DMD), were determined by HPLC. Mean peak serum concentrations (nmol/l) in control patients were 280 for DTZ, 58 for DAD, and 101 for DMD. In cirrhotic patients, the serum DTZ tended to increase and the DAD increased (P<0. 05) while the DMD decreased (P<0.05) compared with that of the control (335 for DTZ, 133 for DAD, and 77 for DMD, nmol/l). Pharmacokinetic analysis using a one-compartment model revealed no change in the absorption but a decrease in the elimination for cirrhotic patients (t1/2, 5. 3 to 7. 2 hr, P<0.1). The elimination rate constant correlated with some biochemical indices for hepatocyte func tion. These results may be explained by the impaired oxidative metabolism of DTZin liver cirrhosis.
