Effect of Pioglitazone on Plasma Levels of Phenytoin in Rats

Introduction: interaction between drugs represents a majorclinical concern for health care professionals and their patients.patients affected by both type 2 diabetes and epilepsy may beprescribed pioglitazone and an anti-epileptic drug such asphenytoin concurrently. the aim of this study was to consider theinteraction of pioglitazone with phenytoin in an experimentalmodel. according to the result of this study concurrent use ofphenytoin and pioglitazone in clinic may cause therapeutic failureof phenytoin which may cause seizures and during seizures thecardiac function may be affected.materials and methods: two groups of rats were treated for 30days. in group 1 (control group) saline (10 ml/kg) and phenytoin(30 mg/kg) were administered daily by intragastric gavage. ingroup 2 (test group), pioglitazone (10 mg/kg) was administereddaily 60 minutes before phenytoin (30 mg/kg). two hours after thelast intragastric gavage, animals were anesthetized with ether and2 ml of blood was drawn from the heart into a syringe containingethylenediaminetetraacetic (edta), and phenytoin concentrationin rat plasma was determined by high performance liquidchromatography (hplc).the study consisted of 2 groups of 10 maleadult wistar rats.results: compared with control group, concurrent use ofpioglitazone and phenytoin was associated with significantly lowermean plasma concentrations of phenytoin: 2.08 ± 0.25 ?g/ml vs 1.2± 0.02 ?g/ml (p < 0.05).conclusion: concurrent use of pioglitazone and phenytoin wasassociated with a significant decrease in plasma concentration ofphenytoin in this experimental model. in clinic, this interaction maycause seizures and it has been shown that both cardiac andrespiratory functions may affected by seizures.