Impaired drug-metabolizing ability in the burned rat.

Research indicating hepatic dysfunction in burn injury led us to investigate the effect of thermal injury on the rat hepatic microsomal drug-metabolizing system. Heated water was used to produce burns corresponding to 15% of the rat's total body surface area. In vitro measurements of p-nitroanisole o-demethylase and aniline hydroxylase activities were significantly depressed on days 1 and 10 postburn. Likewise, in vivo sleeping and paralysis times with pentobarbital and zoxazolamine were significantly prolonged on these same postburn days. On day 10 postburn, the burned rats had significantly decreased levels of urinary D-glucaric acid, a metabolite that correlates with drug metabolizing activity. These results raise the possibility of impaired drug metabolism in human burn victims.