Region-dependent absorption of faropenem shared with foscarnet, a phosphate transporter substrate, in the rat small intestine.
Faropenem, a penem antibiotic, is orally active despite its hydrophilic nature. However, its intestinal absorption has not yet been characterised in detail. This study was undertaken to determine the factors regulating faropenem absorption using intestinal loops prepared in the rat duodenum, jejunum and terminal ileum. Faropenem disappearance was much greater than that of cefotaxime and meropenem, and faropenem disappeared more extensively from the terminal ileum than from the jejunum or duodenum. In contrast to faropenem, the disappearance of ceftibuten was much greater from the duodenum and jejunum than from the terminal ileum. As the accumulation and enzymatic degradation of faropenem was minimal in the intestinal mucosa, faropenem was considered to enter the portal vein smoothly after its disappearance from the intestinal loops. Faropenem disappearance was not significantly influenced by the presence of monocarboxylic acids, amino acids or bile acid. Dipeptides such as L-carnosine and glycylglycine slightly but significantly lowered faropenem disappearance from the terminal ileum. On the other hand, foscarnet exerted a marked inhibitory effect on faropenem disappearance, but the antiviral agent did not modulate ceftibuten absorption. The present results suggest that faropenem is in part absorbed via a phosphate transporter present in the rat small intestine.
Saitoh
Hiroshi
H
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan. saitoh@hoku-iryo-u.ac.jp
Sawazaki
Rinako
R
Oda
Masako
M
Kobayashi
Michiya
M
D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism* / Q000494:pharmacology; D017245:Foscarnet / Q000378:metabolism* / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D028061:Phosphate Transport Proteins / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D047090:beta-Lactams / Q000378:metabolism* / Q000494:pharmacology
D000998:Antiviral Agents; D028061:Phosphate Transport Proteins; D047090:beta-Lactams; D017245:Foscarnet; C107057:fropenem