PT  - JOURNAL ARTICLE
AU  - Surawat Jariyawat
AU  - Takashi Sekine
AU  - Michio Takeda
AU  - Nopporn Apiwattanakul
AU  - Yoshikatsu Kanai
AU  - Samaisukh Sophasan
AU  - Hitoshi Endou
TI  - The Interaction and Transport of β-Lactam Antibiotics with the Cloned Rat Renal Organic Anion Transporter 1
DP  - 1999 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 672--677
VI  - 290
IP  - 2
4099  - http://jpet.aspetjournals.org/content/290/2/672.short
4100  - http://jpet.aspetjournals.org/content/290/2/672.full
SO  - J Pharmacol Exp Ther1999 Aug 01; 290
AB  - In the present study, we investigated the interactions between antibiotics, especially β-lactam antibiotics, and rat renal organic anion transporter 1 (OAT1). [14C]p-Aminohippurate (PAH) uptake via OAT1 expressed in Xenopus laevis oocytes was inhibited by all of the penicillins and cephalosporins tested. Penicillin G, carbenicillin, cephaloridine, cephalothin, cefazolin, and cephalexin inhibited [14C]PAH uptake via OAT1 in a competitive manner (Ki = 0.29–2.33 mM). Cinoxacin, a quinolone gyrase inhibitor, also inhibited PAH uptake via OAT1. Other antibiotics, such as gentamicin, streptomycin, and vancomycin, which do not contain anionic moieties, did not interact with OAT1. [3H]Penicillin G and [14C]cephaloridine were demonstrated to be transported via OAT1. Using the cells that stably expressed OAT1, we analyzed the cytotoxicity of several β-lactam antibiotics. Cells expressing OAT1 showed higher susceptibility to cephaloridine (a potentially nephrotoxic β-lactam antibiotic) toxicity than did control cells. The present study suggests that OAT1 is the major organic anion transporter in the kidney that is responsible for the renal secretion of antibiotics, especially that of β-lactam antibiotics. Furthermore, the culture cell system expressing OAT1 was revealed to be useful for the prediction of the nephrotoxicity of β-lactam antibiotics. The American Society for Pharmacology and Experimental Therapeutics