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We prepared three kinds of morphine suppositories: HE was based on the equivalent mixture of Witepsol H-15 and E-75; S was based on Witepsol S-55 alone; MSC contained controlled-release morphine tablet (MS Contin) in the same base as HE. The pharmacokinetics after rectal administration of the preparations was investigated in rabbits. We found that HE had short Tmax (10min) and that the sustained release continued around 6hr after administration. The extent of bioavailability (BA) of HE was 43.4%, and the plasma concentration of morphine was higher than orally administered MS Contin tablet, throughout the observation period. S had a high BA (95.1%) but Cmax (446.2ng/ml) was too high judged from some risk of adverse effect or dependence. Thus we considered it is not appropriate for clinical use. On the other hand, MSC had longer Tmax (150min). The plasma concentration 12hr after administration was around half the Cmax and the sustained release was found to be good. The MSC's BA also showed high value and only a little dispersion (78.3±6.6%). The cumulative absorption-time profiles of MSC in vivo approximated to the morphine-release behavior of MS Contin tablets in vitro.From the facts described above we conclude:1. We can expect the same or more analgesic effect from HE than oral MS Contin tablets.2. MSC is a good sustained-release morphine suppository which can be expected to be useful for cancer pain therapy, through every 12-hr administration.

Pharmacokinetics of Morphine Following Rectal Administration of Three Kinds of Morphine Suppositories in Rabbits.