Pharmacokinetics of pentobarbital, quinidine, lidocaine, and theophylline in the thermally injured rat.
Previous studies have shown that rats with 15% third-degree burns show a severe depression in various in vitro hepatic drug-metabolizing enzymes. This effect was assessed in vivo by measuring the disposition of four liver-metabolized drugs in 16% third-degree burned rats at 7 d postburn. Compared with pair-fed control rats, pentobarbital demonstrated a significantly prolonged clearance and elimination half-life without a change in volume of distribution. Quinidine demonstrated a significantly increased volume of distribution and a significantly decreased clearance without a change in elimination half-life. Lidocaine showed a significantly increased volume of distribution. Theophylline, which is only 50% metabolized in the rat, showed no changes in any pharmacokinetic parameters. The free drug fractions of quinidine and lidocaine were found to be significantly decreased at 1 d postburn and normal at 7 d postburn. These results warrant pharmacokinetic studies in human burn patients.
D000818:Animals; D002056:Burns / Q000378:metabolism*; D003956:Dialysis; D007700:Kinetics; D008012:Lidocaine / Q000097:blood / Q000378:metabolism*; D008297:Male; D010424:Pentobarbital / Q000097:blood / Q000378:metabolism*; D011802:Quinidine / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013806:Theophylline / Q000097:blood / Q000378:metabolism*
D008012:Lidocaine; D013806:Theophylline; D010424:Pentobarbital; D011802:Quinidine