Hepatic elimination of diazepam: interactions with albumin, desflurane and sevoflurane.
We have studied the effect of sevoflurane and desflurane on the hepatic elimination of diazepam, by incubating slices of rat livers in a closed system. Protein free and protein containing (albumin 10 g litre-1) buffers were used to examine the effect of the anaesthetics on enzyme activity and diazepam binding to albumin. Both anaesthetics (in concentrations of 0.5, 1.5 and 3.0 mmol litre-1) reduced the elimination of diazepam slightly in the absence of albumin, while the presence of the protein increased elimination to a maximum of 30% at the greatest concentration of the anaesthetics. These data support previous observations that volatile anaesthetics may interact pharmacokinetically with both liver enzyme activity and drug binding to albumin.
Dale
O
O
University of Trondheim, Department of Pharmacology and Toxicology, University Clinic, Norway.
Frink
E J
EJ
Thommesen
L
L
Gandolfi
A J
AJ
D000418:Albumins / Q000378:metabolism; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D000077335:Desflurane; D003975:Diazepam / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004987:Ethers / Q000494:pharmacology*; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008297:Male; D008738:Methyl Ethers; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane
D000418:Albumins; D000777:Anesthetics; D004987:Ethers; D008738:Methyl Ethers; D000077149:Sevoflurane; D000077335:Desflurane; D007530:Isoflurane; D003975:Diazepam