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British Journal of Anaesthesia, 1988, Vol. 60, No. 6 692-696
© 1988 The Board of Management and Trustees of the British Journal of Anaesthesia

research-article

RAT LIVER SLICES AND DIAZEPAM METABOLISM: IN VITRO INTERACTIONS WITH VOLATILE ANAESTHETIC DRUGS AND ALBUMIN{dagger}

O. DALE, M.D., PH.D.,*, A. J. GANDOLFI, PH.D.,, K. BRENDEL and S. SCHUMAN

(Department of Anesthesiology); (Department of Pharmacology) ; College of Medicine, University of Arizona Tucson, Az 85724, U.S.A.

*Present address, for correspondence: Department of Anesthesiology, Regional Hospital, University of Trondheim, 7006 Trondheim, Norway.

The influence of the volatile anaesthetic agents enflurane, isoflurane, halothane and the halothane metabolite trifluoroacetic acid was studied on the hepatic elimination of diazepam, by incubating precision-cut slices of rat liver in a closed system. The impact of anaesthetic-induced action on enzyme activity and diazepam binding to human serum albumin (HSA) was assessed in protein free and protein containing buffers, respectively. Human serum albumin reduced the elimination of diazepam by 12 and 50% at concentrations of 1 and 10 mg ml–1, respectively. In the absence of albumin, halothane 1 mmol litre–1 reduced the elimination of diazepam by 13%, whereas enflurane at 1.5 mmol litre–1 caused a reduction of 8%. No effect was seen from isoflurane 1 mmol litre–1 and trifluoroacetic acid 4 mmol litre–1. In the presence of the highest concentration of albumin, however, an increased elimination of diazepam of 24% resulted from exposure to enflurane and trifluoroacetic acid, while no statistically significant changes were seen for isoflurane and halothane. The present work supports the view that volatile anaesthetic agents may cause pharmacokinetic drug interactions by interference with both enzyme activity and drug protein binding.

{dagger}Presented in part at the ASPET-SOT Meeting, Baltimore MD, August 17–21, 1986; FASEB Meeting Washington DC, March 29–April 3, 1987, and 19th Congress of the Scandinavian Society of Anaesthesiologists, Linköping, Sweden, June 29–July 3, 1987.


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Home page
 Toxicol PatholHome page
A. J. Gandolfi, J. Wijeweera, and K. Brendel
Use of Precision-Cut Liver Slices as an In Vitro Tool for Evaluating Liver Function
Toxicol Pathol, January 1, 1996; 24(1): 58 - 61.
[Abstract] [PDF]


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