![Sample our Bioscience journals, sign in here to start your access, Latest two full volumes FREE to you for 14 days]({"type":"image" , "src" : "/sda/5925/TOC-Subject-Sample-2021-Bioscience.jpg"})
Abstract
1. The metabolism of aminopyrine has been investigated in normal, alloxan- and streptozotocin (STZ)-diabetic rats. The drug was administered i.p. and the serum concentrations of the unchanged aminopyrine and its main metabolites were measured using h.p.l.c.
2. Aminopyrine was metabolized at a slower rate in both diabetic rats, as judged from higher serum levels of the unchanged drug. Pharmacokinetic studies of aminopyrine in diabetic rats also showed a decrease in serum clearance of the drug and an increase in us serum half-life.
3. The serum concentrations of the metabolites 4-monomethylaminoantipyrine. 4-acetylaminoantipyrine and 4-formylaminoantipyrine decreased in diabetic rats. In contrast, serum levels of 3-hydroxymethyl-2-methyl-4-dimethylamino-1-phenyl-3-pyrazolin-5-one increased over control values. Serum concentrations of 4-aminoantipyrine remained unaltered by the induction of diabetes.
4. The magnitudes of changes in serum levels of these metabolites were larger in alloxan-diabetes than in STZ-diabetes.
5. Additional support for changed metabolism of aminopyrine was obtained from the investigation of microsomal preparations from diabetic and normal rats.
6. These findings indicate that it is important to use intact animals for evaluation of the metabolism of drugs in pathological states.