Application of nifedipine sustained-release suppositories to healthy volunteers.

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Abstract
Double layer suppositories (D-15) of nifedipine (NF), prepared by using a solid dispersion system of polyethylene glycol 4000 as a water-soluble carrier and cellulose acetate phthalate as a poorly water-soluble carrier, were administered to healthy volunteers, and their sustained-release characteristics, bioavailability and clinical utility were investigated. It was found that D-15 was able to maintain a therapeutically effective level of NF from 30 min to 10h without causing an excessively high peak level and offered good bioavailability. From the results of pharmacokinetic analysis by using the compartment model method, it appeared that the plasma concentration-time course after rectal administration of D-15 is satisfactorily accounted for by a one-compartment model with first-order release and absorption steps. The value of release rate constant of D-15 obtained was smaller than that of absorption rate constant, and the sustained-release effect was apparently atttributed to the slow release of NF from the suppository. The plasma level of NF rapidly decreased as removing D-15, and the plasma level showed hardly any irregularities arising from the removal and the renewal of suppositories. Accordingly, it was concluded that D-15 is an effective sustained-relase dosage from and represents a convenient mode of therapy with reduced frequency of drug administration and reduced risk of side-effects.