Pharmacokinetics of phenytoin were studied in healthy subjects. In a crossover study five volunteers received either a single oral dose (300 mg) of phenytoin alone or in combination with multiple doses of piperine (20 mg × 7 days) followed by an oral dose of phenytoin. Blood samples were collected at 0.5, 1,2,3,4,8,12,24, and 48 h after drug administration and analysed for phenytoin by the enzyme multiplied immunoassay technique (EMIT). The results obtained revealed that a single daily dose of piperine for 7 days decreased the absorption halflife (P < 0.05), prolonged the elimination halflife (P < 0.01), and produced a higher area under the drug concentration curve (P < 0.05) in comparison to phenytoin alone. It is therefore concluded that piperine on multiple dose administration alters the pharmacokinetic parameters of the antiepileptic.
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Amla et al. (1987) studied this question.