UTILITY OF A RECTAL SUPPOSITORY CONTAINING THE ANTIEPILEPTIC DRUG ZONISAMIDE

A suppository of zonisamide (ZNS) was investigated from the viewpoint of pharmaceutical evaluation, pharmacokinetics and pharmacological eff ect, Two types of ZNS suppositories were prepared, One used Witepsol ( H-15:S-55 = 3:1) as a lipophilic base and the other polyethylene glyco l (PEG, 4000:1500 = 4:1) as a hydrophilic base, The in vitro release r ate of ZNS from the PEG suppository was significantly rapid compared w ith that of ZNS from Witepsol. Male Wistar rats were administered ZNS (20 mg/kg) using an intravenous, oral or rectal (PEG or Witepsol) rout e, The absorption of ZNS from the PEG suppository was more rapid than that of ZNS from the Witepsol suppository or from the oral preparation , The peak plasma concentration (C-max) after a rectal administration of ZNS with Witepsol or PEG suppository was significantly higher than that after the oral administration of ZNS, However, the bioavailabilit y of the three preparations was approximately 100%, Male ICR mice were administered ZNS (80 mg/kg) using the oral or rectal (PEG or Witepsol ) route, A positive correlation was observed between the electroshock seizure (ES) threshold and ZNS concentration in plasma or brain, Furth er, there was no significant difference in the ES threshold or the ZNS concentration in plasma or brain among the three preparations, These results indicate that a ZNS suppository is a very useful preparation f rom the view point of both pharmacokinetics and pharmacological action .