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.
University of Trondheim, Department of Pharmacology and Toxicology, University Clinic, Norway.
O
O
Dale
E J
EJ
Frink
L
L
Thommesen
A J
AJ
Gandolfi
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