Abstract
Drug interactions between phenytoin and rosuvastatin may occur when used together in normal rats, so the present study was conducted to investigate the effects of the individual as well as combined drugs were studied in normal rats. Rats were divided into 4 groups namely: normal control, phenytoin (60 mg/kg i.p.), rosuvastatin (1.25 mg/kg i.p.) or combination of both phenytoin and rosuvastatin, respectively. Data of the present work revealed that, phenytoin increased serum total cholesterol. Rosuvastatin didn’t affect serum total cholesterol or serum triglycerides. Combination increased serum total cholesterol but it didn’t affect serum triglycerides. Phenytoin significantly increased serum LDL-C. Rosuvastatin had no effect on serum HDL-C, serum LDL-C and VLDL-C levels. Combination didn’t change serum lipoproteins (HDL-C, LDL-C and VLDL-C). Individual drugs or their combination had no effect on risk factor and atherogenic index. Phenytoin significantly increased serum ALT level. Rosuvastatin had no effect on serum AST and serum ALT levels. Combination significantly increased serum AST level. Phenytoin significantly increased serum MDA level but it had no effects on serum NO level and blood SOD activity. Rosuvastatin significantly increased serum NO level. Combination significantly increased serum NO level, so Combination of phenytoin and rosuvastatin has a good effect on oxidative stress by increasing serum NO level. In conclusion, the results revealed that, there are drug interactions between phenytoin and rosuvastatin. The interactions improve liver functions and lipid peroxidation. A part from the action of the combination on total cholesterol, it improves lipid profile.
Highlights
Phenytoin (PHT) is a classical antiepileptic drug
PHT is most commonly used to reduce seizure frequency including seizure associated with acute brain lesions (Woodbury et al, 1982)
It has a narrow therapeutic index and a change in bioavailability with other drugs or supplements administered concurrently may lead to toxic effects or therapeutic failure (Arnold et al, 1970).There is great interest to study the interactions of phenytoin with other drugs because of its enzyme inducing effects and special physiochemical and solubility properties (Potsalos et al, 2002; Lalonde and Botez, 1958)
Summary
Phenytoin (PHT) is a classical antiepileptic drug. PHT is effective mainly against focal epileptic seizures and against generalized tonicclonic convulsions. PHT is most commonly used to reduce seizure frequency including seizure associated with acute brain lesions (Woodbury et al, 1982). It has a narrow therapeutic index and a change in bioavailability with other drugs or supplements administered concurrently may lead to toxic effects or therapeutic failure (Arnold et al, 1970).There is great interest to study the interactions of phenytoin with other drugs because of its enzyme inducing effects and special physiochemical and solubility properties (Potsalos et al, 2002; Lalonde and Botez, 1958)
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