Biotransformation of halothane in guinea pig liver slices.
The biotransformation of halothane was studied using liver slices. Precision-cut Hartley male guinea pig liver slices (1 cm diameter; 250-300 microns thick) were incubated in sealed roller vials containing supplemented Krebs-Henseleit buffer at 37 degrees C under different O2 tensions (2.5, 21, and 95%). After a 1-hr preincubation, halothane was vaporized in the vial producing a 1.9 mM medium concentration. Halothane metabolites (Br-, trifluoroacetic acid, F-) were measured at 2, 4, and 6 hr. Viability of the incubated slices was verified by determining intracellular K+ content and levels of cytochrome P-450, which were maintained under 95% O2 atmosphere but decreased with lower O2 tensions (2.5%). The highest fluoride production was 300 +/- 22 pmol/mg slice weight/6 hr at low O2 tension (2.5%). Defluorination decreased with increasing O2 tension to undetectable levels under 95% O2. Production of the oxidative metabolite, trifluoroacetic acid, was highest at 95% O2 (2.35 +/- 0.17 nmol/mg slice weight/6 hr). Trifluoroacetic acid production decreased with decreasing O2 tension. Br- production was the highest at 21% O2 (1.8 +/- 0.13 nmol/mg slice weight/6 hr). Production of Br- was not dependent on the O2 tension. The guinea pig slices are capable of biotransforming halothane (oxidative/reductive); therefore, this in vitro system appears suitable for studying the biotransformation of halothane.
Ghantous
H N
HN
Department of Anesthesiology, University of Arizona, Tucson 85724.
Fernando
J
J
Gandolfi
A J
AJ
Brendel
K
K
D000818:Animals; D001274:Atmospheric Pressure; D001711:Biotransformation; D001965:Bromides / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005459:Fluorides / Q000378:metabolism; D006168:Guinea Pigs; D006221:Halothane / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D011188:Potassium / Q000378:metabolism; D014269:Trifluoroacetic Acid / Q000378:metabolism
D001965:Bromides; D002245:Carbon Dioxide; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D014269:Trifluoroacetic Acid; D005459:Fluorides; D011188:Potassium; D006221:Halothane