Stereoselective Inhibition of Renal Basolateral Human Organic Anion Transporter 3 by Lansoprazole Enantiomers.
Pharmacology
; 101(3-4): 176-183, 2018.
Article
em En
| MEDLINE
| ID: mdl-29353278
ABSTRACT
Lansoprazole, a proton pump inhibitor, potently inhibits human organic anion transporter, hOAT3 (SLC22A8). Lansoprazole has an asymmetric atom in its structure and is clinically administered as a racemic mixture of (R)-and (S)-enantiomers. However, little is known about the stereoselective inhibitory potencies of lansoprazole against hOAT3 and its homolog, hOAT1. In the present study, the stereoselective inhibitory effect of lansoprazole was evaluated using hOAT1-and hOAT3-expressing cultured cells. hOAT1 and hOAT3 transported [14C]p-aminohippurate and [3H]estrone-3-sulfate (ES) with Michaelis-Menten constants of 29.8 ± 4.0 and 30.1 ± 9.0 µmol/L respectively. Lansoprazole enantiomers inhibited hOAT1- and hOAT3-mediated transport of each substrate in a concentration-dependent manner. The IC50 value of (S)-lansoprazole against hOAT3-mediated transport of [3H]ES (0.61 ± 0.08 µmol/L) was significantly lower than that of (R)-lansoprazole (1.75 ± 0.31 µmol/L). In contrast, stereoselectivity was not demonstrated for the inhibition of hOAT1. Furthermore, (S)-lansoprazole inhibited hOAT3-mediated transport of pemetrexed and methotrexate (hOAT3 substrates) more strongly than the corresponding (R)-lansoprazole. This study is the first to demonstrate that the stereoselective inhibitory potency of (S)-lansoprazole against hOAT3 is greater than that of (R)-lansoprazole. The present findings provide novel information about the drug interactions associated with lansoprazole.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transportadores de Ânions Orgânicos Sódio-Independentes
/
Inibidores da Bomba de Prótons
/
Lansoprazol
Limite:
Humans
Idioma:
En
Revista:
Pharmacology
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Japão