Burn Injury to Mice Inhibits Drug Metabolism and Prolongs Sleep Time

Abstract

Treatment of pain associated with burn injury is a major clinical challenge, which is particularly complicated due to changes in drug metabolism associated with thermal injury. In the present study, we have examined drug metabolism in mice subjected to thermal injury. Mice (CD-1, Charles River, male, 28 grams) were anesthetized with ether, the dorsum shaven and subjected to thermal injury (20 % TBSA, 90oC, 9 seconds) followed by saline resuscitation (2 mL, IP). Drug induced sleep times were determined by treating mice at 24 hours post burn with pentobarbital (60 mg/kg, IP), ketamine (40 mg/kg, IP), or ether, in which case the mice were placed in a bell jar with ether saturated atmosphere. In another group of mice at 24 hours post burn, exhaled 14CO2 was collected in vivo to determine oxidation of 14C-aminopyrine. Mice were injected with 0.5 microcuries of 14C-aminopyrine and immediately placed...