Study of Pharmacokinetic Interaction of Ascorbic Acid and Phenytoin in Rats



Minaiyan M^{1, 2} ; Ghafghazi T¹ ; Majdzadehardakani M² Show Affiliations
Source: Daru Published:2008

Abstract

Background and purpose of the study: There is great interest for researchers and therapists to study the interactions of phenytoin with other drugs or foods because of its enzyme inducing effects, saturable biodisposition and specific physicochemical properties. There are reports indicating that ascorbic acid (ASC) affects interacting properties of phenytoin. By considering pharmacokinetic aspects, the present study was carried out to evaluate the effect of ASC on single and multiple dose kinetics of phenytoin in rats. Methods: Male Wistar rats weighting 200-225 g were randomly divided into 9 groups of 6. In groups 1 to 3, phenytoin was administered orally (p.o.) (30 mg/kg) for a week and saline (5 ml/kg) and ASC (200, 500 mg/kg) were given p.o. one hour before each phenytoin treatment respectively. In groups 4 and 5, animals were treated with saline and ASC (500 mg/kg) for a week and one hour before single dose of phenytoin (30 mg/kg). In groups 6 and 7, single dose of phenytoin was administered p.o. (60 mg/kg) whereas normal saline and ASC (500mg/kg) were administered concurrently intraperitoneally (i.p.). In groups 8 and 9, single dose of phenytoin (60 mg/kg) was administered i.p., whereas other treatments were similar to groups 6 and 7. Blood samples were taken at 0, 1, 2, 3, 4, 6, 8 and 12 hours after phenytoin administration and analyzed by HPLC method. Results: It was found that AUC0-∞, AUC0-t, Cmax, Tmax, and T1/2 didn't change significantly in the test groups compared to the respected controls. T max and T1/2 were only parameters showed a significant increase in groups 3 and 5 compared to control groups. Acidic change in gut lumen and/or renal tubules may explain these interactions. Conclusion: Results of this study indicate that ASC has no significant interaction with phenytoin bioavailability.