Microsomal drug-metabolizing enzyme activity in rats given α-(2,4-dichlorophenyl)-α-phenyl-5-pyrimidinemethanol for periods of 14 days to 2 years

Abstract

The dose-response relationships for stimulation of hepatic drug-metabolizing enzymes were studied in rats given α-(2,4-dichlorophenyl)-α-phenyl-5-pyrimidinemethanol (EL-273) in the diet for periods of 2 weeks-2 years. The dietary concentrations ranged from 20 to 5000 ppm. p-Nitroanisole metabolism was not affected by EL-273 concentrations of 80 ppm or less. With dietary concentrations of 160–1250 ppm the rate of metabolism increased in proportion to the log of the dose. Concentrations greater than 1250 ppm produced no additional increase. Above a threshold of 80 ppm, EL-273 increased relative liver weight and microsomal protein. The effects of EL-273 on the liver at 2 weeks were reversible within 2 weeks on control diet. In chronic tests the increases in relative liver weight and p-nitroanisole metabolism reached maxima after 2 weeks of EL-273 administration and remained relatively constant throughout the remainder of the 2-year test.