ϵ-Acetamidocaproic acid pharmacokinetics in rats with gastric ulcer or small bowel inflammation

Abstract

The pharmacokinetics of ϵ-acetamidocaproic acid (AACA) were evaluated after the intravenous and oral administration of an antiulcer agent, zinc acexamate (ZAC) at a dose of 20 mg kg−1 (ion pairing between zinc and AACA) in rats with indomethacin-induced acute gastric ulcer (IAGU) or indomethacin-induced small bowel inflammation (ISBI).In IAGU rats, the area under the curves (AUCs) of AACA were significantly smaller after both the intravenous (551 versus 1270 μg min ml−1) and oral (397 versus 562 μg min ml−1) administration of ZAC than controls, possible due to the significantly faster CLR of AACA. In ISBI rats, however, the AUCs of AACA were comparable with controls after both the intravenous and oral administration of ZAC.In IAGU rats, the significantly smaller AUCs of AACA were due to the significantly faster CLR (due to the decreased urinary pH by indomethacin treatment) than controls. AACA has a basic secondary amine group. On the other hand, the comparable AUCs of AACA in ISBI rats were due to the comparable CLRs between ISBI and control rats.AACA was excreted in the urine via active renal tubular secretion in all rats studied.