The biotransformation of acetophenetidin in the alloxan-diabetic rabbit☆

Abstract 1. 1. The rate of acetophenetidin metabolism has been investigated in normal and alloxan-diabetic rabbits. 2. 2. The drug was metabolized at a slower rate in the diabetic rabbits after oral or intraperitoneal administration, as judged by the higher level of unchanged compound as well as by the lower levels of the de-ethylated (NAPA) and conjugated derivatives in plasma and urine of this group. 3. 3. The differences in the rates of biotransformation of the drug were more pronounced in the severely diabetic rabbits. 4. 4. Treatment of the diabetic rabbits with insulin reverted the pattern of disposition of acetophenetidin and its metabolites to near normality. 5. 5. Evidence is produced to support the thesis that the observed depressed metabolism of acetophenetidin in the alloxan-diabetic rabbit could mainly be due to a deficiency of reduced nicotinamide-adenine dinucleotide (NADPH) and/or microsomal drug-metabolizing enzyme protein, in addition to a defective glucuronide-conjugating system as a result of the diabetic state.