RT Journal Article
SR Electronic
T1 Mechanism of Intestinal Absorption of an Orally Active β-Lactam Prodrug: Uptake and Transport of Carindacillin in Caco-2 Cells
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 958
OP 964
VO 290
IS 3
A1 Yin-Hua Li
A1 Kiyomi Ito
A1 Yasuyuki Tsuda
A1 Rikako Kohda
A1 Hideo Yamada
A1 Tomoo Itoh
YR 1999
UL http://jpet.aspetjournals.org/content/290/3/958.abstract
AB Absorption characteristics of carindacillin (CIPC) were investigated using Caco-2 cells, and the results were compared with those of its parent drug, carbenicillin (CBPC). Uptake of CBPC was not affected by the metabolic inhibitor or the change in extracellular pH. CBPC appeared to be taken up into Caco-2 cells by passive diffusion. In contrast, the uptake of CIPC was greater at lower extracellular pH and was inhibited in the presence of carbonyl cyanidep-(trifluoromethoxy)phenyl hydrazone, a protonophore. Also, transport of CIPC through Caco-2 cell monolayer was energy and temperature dependent. Moreover, the uptake and transport of CIPC were significantly inhibited in the presence of various monocarboxylic acids, which are the substrates of the monocarboxylic acid transport system(s), whereas the substrates of the oligopeptide transporter had no effect on the uptake or transport of CIPC. These results suggested that the absorption of CIPC may be mediated by the monocarboxylic acid transport system(s), not by the oligopeptide transporter. Furthermore, the uptake and transport of CIPC were approximately 40-fold greater than those of CBPC. Therefore, it is likely that the participation of a carrier-mediated transport in the absorption of CIPC may significantly contribute to the improved absorption of the prodrug over the parent drug. The American Society for Pharmacology and Experimental Therapeutics