Effect of Simultaneous Insertion of Oleaginous Base on the Absorption and on the Anticonvulsant Effect of Diazepam Suppository

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  • Effect of Simutaneous Insertion of Oleaginous Base on the Absorption and on the Anticonvulsant Effect of Diazepam Suppository

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To clarify the drug-base interaction between diazepam (DZP) suppository and oleaginous base, we investigated the effect of simultaneous combination of oleaginous base on the absorption and on the anticonvulsant effect of DZP Suppository in rats. Simultaneous insertion of DZP suppository and oleaginous base significantly decreased maximum concentration (Cmax) and area under the blood concentration–time curve (AUC) of plasma DZP concentrations. Administration of DZP suppositories (2.5, 5 mg/kg) dose-dependently suppressed the pentylenetetrazol (PTZ)-induced seizures, and the anticonvulsant effect of DZP suppository (5 mg/kg) was reduced by simultaneous insertion of oleaginous base. In an in vitro study using a suppository release apparatus, simultaneous combination of DZP suppository and oleaginous base (1.5—98 mg) significantly decreased the accumulative release of DZP in a dose-dependent manner. These results suggested that when DZP suppository and oleaginous base are inserted simultaneously, the released DZP distributes partially to the oleaginous base, and this phenomenon is related to the decreases in the plasma concentration and the anticonvulsant effect of DZP.

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