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In order to estimate the application to rectum of calcium and magnesium salts of indomethacin (IND), the suppositories of the salts and IND were prepared using macrogol and Witepsol H-15 bases. The rectal administration of these suppositories (Witepsol H-15) was compared with the oral administration of IND and the salts. The hardness, melting point, and liquefaction time of the suppositories were similar between IND and the salts. The in vitro release of IND-Mg from the suppositories was significantly faster than that of IND, while the release of IND-Ca was slower. The area under the plasma drug concentration-time curve (AUC) after IND suppositories was significantly higher than that after oral administration of IND (p less than 0.01). The AUC value after IND-Ca suppositories was slightly higher than those after other suppositories, although the plasma levels in early period after IND-Ca suppositories were lower, indicating the slow absorption of IND-Ca. The multiple treatment with IND-Ca suppositories gave no histological change of the rectal mucosa. Therefore, the present results suggested that IND-Ca was favourable for the rectal administration, in high doses and repeatedly.

Absorption and bioavailability of calcium and magnesium salts of indomethacin from rectal suppositories.