未熟児動脈管開存症治療のためのメフェナム酸坐剤の開発と評価：基剤による放出制御と健常人における体内動態

Abstract

Two types of mefenamic acid (MA) suppositories were prepared, one with Vosco®, an oleaginous base (Vosco suppository) and another with polyethylene glycol (PEG), a watersoluble base (PEG suppository). The crystallinities of MA in the Vosco and PEG suppositories, the in vitro release behaviors of MA from them, and the pharmacokinetics of MA following their rectal administarations to healthy volunteers were respectively compared. X-ray diffractometry revealed that MA in the Vosco suppository was mainly dispersed in a crystal form, whereas MA in the PEG suppository was disseminated in the amorphous state, with the in vitro release of MA from the PEG suppository being faster. MA in the Vosco or PEG suppository was chemically stable, and the in vitro release behavior of MA from each suppository did not change after storage for 2 months at 5°C. The serum MA maximum concentration (Cmax) and the time to reach Cmax after rectal administration of the PEG suppository appeared to be respectively higher and to be shorter than those of the Vosco suppository. The areas under the serum MA concentration-time curves (AUCs) from zero time to 8 h for the Vosco and PEG suppositories were 3.2 and 4.1 μg·h/ml, respectively, and their values were not significantly different. It was concluded that the PEG suppository presented a faster release characteristic of MA than did the Vosco suppository and that the serum MA concentration profiles arising after administration of these suppositories reflected their release characteristics.