Acute hepatic damage in rats impairs metharbital metabolism

Metharbital metabolism was impaired in rats after acute hepatic damage induced by carbon tetrachloride. Compared to control rats, hepatic damage prolonged the metharbital sleeping time and reduced the slopes of log metharbital plasma concentration-time curves. Renal contributions to metharbital elimination from plasma were negligible since only about 6% of the metharbital administered was eliminated unchanged in urine. In rats with hepatic damage, metharbital clearance from plasma and elimination of its demethylated metabolite, barbital, in urine decreased with increasing severity of damage. These results indicate that the kinetics of both metharbital and its metabolite reflect sensitively hepatic drug-metabolizing capacity. Measuring urinary elimination of barbital, following metharbital administration, may serve as a convenient laboratory test to evaluate the hepatic drug-metabolizing capacity.