Pharmacodynamic and pharmacokinetics of metronidazole in protein malnourished rats

The aim of this study is to evaluate the relationships between metronidazole toxicity and pharmacokinetics in protein malnourished rats. The study was carried out on two sets of rats, normally-fed set and protein malnourished set. Each set was divided into a control group and three-treated groups that received metronidazole daily in one dose of 200, 400 or 800 mg/kg for 30 days. Liver enzymes as well as testosterone and gonadotropin hormones levels were estimated. The pharmacokinetic profiles were carried out over a period of 48 h. Metronidazole plasma levels were determined by a validated high-performance liquid chromatography (HPLC) method. Metronidazole has dose dependent effects on hematological profile, liver enzymes, testosterone and gonadotropins which potentiated in protein malnourished rats. Protein malnutrition elevated metronidazole Cmax, AUC0-48, and AUC0-inf, prolonged t1/2 and MRT, and decreased elimination rate constant. The clinical significance of this work should be stressed in case of protein malnourished individuals due to the risk of accumulation of the drug after repeated doses.   Keywords: Protein malnutrition, rats, Metronidazole, pharmacokinetics, pharmacodynamic, Carbamazepine.