Linear relationship between cytochrome P-450 and carbamazepine clearance in rhesus monkey.
The effect of carbamazepine (CBZ) long-term (4-day) infusions on changes in liver cytochrome P-450 levels were examined in eight rhesus monkeys. Each animal received two treatments. Treatment I was a 4-hr CBZ infusion and treatment II was a 4-day CBZ infusion. At the end of each treatment, the monkey was anesthetized and a liver biopsy was taken. The tissue was homogenized and cytochrome P-450 and protein were determined in the crude liver homogenate. During treatment II, blood samples taken at 8 and 101 hr were assayed for CBZ and the clearance of CBZ at these times determined. The mean (+/- SD) CBZ clearance at 8 and 101 hr during treatment II was 0.88 +/- 0.17 and 1.35 +/- 0.34 liters/hr/kg, respectively. The mean (+/-SD) liver cytochrome P-450 level between treatment I and treatment II was 0.26 +/- 0.04 and 0.44 +/- 0.14 nmol/mg of protein, respectively. A high degree of correlation (r2 = 0.85) was observed between the percentage change in cytochrome P-450 and the percentage change in CBZ intrinsic clearance. Theoretical and experimental results suggest a direct quantitative relationship between these parameters.
D000818:Animals; D002220:Carbamazepine / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D011506:Proteins / Q000378:metabolism
D011506:Proteins; D002220:Carbamazepine; D003577:Cytochrome P-450 Enzyme System