Effects of Shousaiko-to, Keishikashakuyaku-to and its Simultaneous Use on the Pharmacokinetics of Phenytoin in Rabbit.

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Abstract
It is supposed that the potentiation of an antiepileptic action which is clinically found by using phenytoin with both Shousaiko-to (T-9) and Keishikashakuyaku-to (T-60) (: T-9+ 60) might have to be caused by the change of pharmacokinetics of phenytoin. In order to estimate the effect of Kampo extracts, the influence on the pharmacokinetic parameters of phenytoin at 7 days after the oral administration of these three Kampo extracts of T-9, T-60 and T-9+60 was studied in rabbits.In the treatment-groups of T-9 and T-9+60, the values of serum total (Ct) and free (Cf) phenytoin concentrations and half-life (T1/2) decreased. Total serum clearance (Cl) of phenytoin increased, and Cf/Ct and volume of distribution of phenytoin did not change. However, in the treatment-groups of T-60, all the pharmacokinetic parameters of phenytoin estimated did not produce any significant changes. These results suggest that the decrement of serum phenytoin concentration induced by the treatment with T-9+60 might mainly be due to the stimulation of hepatic phenytoin-oxidizing metabolic enzyme activity by T-9. The potentiation of the antiepileptic effect induced by the combination therapy of phenytoin and T-9+60 would not result in the increment of serum phenytoin concentration, but an independent pharmacological effect of phenytoin and T-9+60.

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