Study of the bioavailability of four indomethacin suppository formulations in healthy volunteers

Abstract

The bioavailability of four different 100 mg indomethacin suppository formulations was determined in healthy male volunteers. Two marketed formulations, Indocid ® and Dolcidium ®, and a triglyceride (Witepsol H 15) supplemented with 5% monoglycerides (Dim. LS) or 9% fatty acids and 1% fatty acid methyl esters (FA/FAME) were included in the study. The AUC 0−12h (μg h ml −1) was (mean ± S.D.) 9.51 ± 4.06 8.96 ± 2.55, 10.78 ± 5.64 and 11.01 ± 5.07 for the Indocid ®, Dolcidium ®, Dim. LS and FA/FAME formulations, respectively. The bioavailability parameters for the marketed formulations were comparable to those reported for similar formulations in the literature. The values of the two supplemented triglyceride formulations were not significantly different from those obtained from the reference formulation, Indocid ®. As the addition of monoglycerides and fatty acid-fatty acid methyl esters to a triglyceride suppository base not only enhances rectal absorption but also reduces rectal mucosal irritation in rabbits, these additives might be useful for rectal drug administration. However, further experiments with larger groups of volunteers or patients, using multiple applications, are necessary in order to reveal the suitability and safety of these excipients as alternatives for those presently used in suppository formulations.