Possible Factors Involved in Oral Inactivity of Meropenem, a Carbapenem Antibiotic

Toshihide Saito, Rinako Sawazaki, Kaori Ujiie, Masako Oda, Hiroshi Saitoh

Department of Pharmaceutics, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan.
Department of Pharmaceutics, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan..

DOI: 10.4236/pp.2012.32027                

Abstract

Meropenem, a carbapenem antibiotic, is inactive after oral administration and administered exclusively by injection. In this study, in order to address the factors involved in the oral inactivity of meropenem, in vitro permeation characteristics across rat ileal segments was investigated using diffusion cells. Moreover, stability of meropenem was evaluated in the Japanese Pharmacopoeia (JP) 1^st and 2^nd fluid for disintegration test. Cefotaxime, ceftibuten, and faropenem were used for comparison. The permeation of meropenem across rat ileal segments was approximately 5-fold greater in secretory direction than in absorptive direction. The secretory-oriented transport of meropenem markedly diminished by replacement of D-glucose in the experimental medium with unmetabolizing 3-O-methyl-D-glucose, suggesting that the secretory transport of meropenem was an energy-dependent process. Cefotaxime exhibited extensively secretory-oriented permeation. On the other hand, much weaker directionalities were observed in ceftibuten and faropenem. While meropenem as well as other three β-lactam antibiotics was stable in JP 2^nd fluid (pH 6.8), it declined rapidly in JP 1^st fluid (pH 1.2). These results suggest that, in addition to the hydrophilic property of meropenem, its instability at gastric pH and secretory transport in the small intestine are possible factors involved in the inactivity of meropenem after oral administration.

Keywords

Meropenem, Oral inactivity, Secretory transport, Degradation, Gastric pH

Conflicts of Interest

The authors declare no conflicts of interest.

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