Liver Disease and Drug Metabolism

Conventional wisdom holds that clinicians should give low doses of medications metabolized by the liver (i.e., most psychotropic drugs other than lithium and some anticonvulsants) to patients with liver disease because they metabolize these drugs very slowly. These researchers used established probes to examine activity of cytochrome P450 (CYP) enzymes 1A2, 2C19, 2D6, and 2E1 in 20 patients in various stages of hepatitis B or C, chemically induced hepatitis, alcoholic or cryptogenic cirrhosis, or primary sclerosing cholangitis. Twenty controls were matched for age, weight, and sex.

Compared with controls, patients with compensated liver disease had lower activity of CYP2C19 but not of the other enzymes. Reduced activity of all four enzymes w…