[Metabolism of hypnotic and sedative drugs in cholestasis (author's transl)].

Alterations of hepatic microsomal biotransformation in cholestasis were discussed. In experimental animals biotransformation of hypnotic and sedative drugs is impaired under cholestatic conditions in vivo. The endplasmic reticulum of the hepatocytes is hypertropic but is hypoactive with respect to drug metabolism, a condition which is partly due to interference to substances retained in cholestatic livers (bile salts) with drug biotransformation and to cytochrome P-450 diminution in the microsomal membranes. The activity of conjugating enzymes (phase II of biotransformation) remains unaffected. A similar situation exists in cholestatic patients in which drug elimination is altered. In vitro studies with human liver homogenate, microsomes, and liver slices confirm the animal experiments by showing that cytochrome P-450 as well as the metabolism of hypnotics are reduced in cholestasis.