Search

Your search keyword '"Inui, Ken-ichi"' showing total 45 results
Start Over Author "Inui, Ken-ichi" Journal pharmaceutical research
45 results on '"Inui, Ken-ichi"'

37. Investigation of Endogenous Compounds for Assessing the Drug Interactions in the Urinary Excretion Involving Multidrug and Toxin Extrusion Proteins

Author

Kato, Koji, primary, Mori, Haruyuki, additional, Kito, Tomoko, additional, Yokochi, Miyu, additional, Ito, Sumito, additional, Inoue, Katsuhisa, additional, Yonezawa, Atsushi, additional, Katsura, Toshiya, additional, Kumagai, Yuji, additional, Yuasa, Hiroaki, additional, Moriyama, Yoshinori, additional, Inui, Ken-ichi, additional, Kusuhara, Hiroyuki, additional, and Sugiyama, Yuichi, additional

Published
2013
Full Text
View/download PDF

44. Investigation of Endogenous Compounds for Assessing the Drug Interactions in the Urinary Excretion Involving Multidrug and Toxin Extrusion Proteins.

Author

Kato, Koji, Mori, Haruyuki, Kito, Tomoko, Yokochi, Miyu, Ito, Sumito, Inoue, Katsuhisa, Yonezawa, Atsushi, Katsura, Toshiya, Kumagai, Yuji, Yuasa, Hiroaki, Moriyama, Yoshinori, Inui, Ken-ichi, Kusuhara, Hiroyuki, and Sugiyama, Yuichi

Subjects
DRUG interactions, MULTIDRUG resistance, EXCRETION, URINARY organ examination, ORGANIC cation transporters, BIOMARKERS
Abstract

Purpose: Multidrug and toxin extrusion proteins (MATEs) are multispecific organic cation transporters mediating the efflux of various cationic drugs into the urine. The present study aimed at identifying endogenous compounds in human plasma and urine specimens as biomarkers to evaluate drug interactions involving MATEs in the kidney without administration of their exogenous probe drugs. Methods: An untargeted metabolomic analysis was performed using urine and plasma samples from healthy volunteers and mice treated with or without the potent MATE inhibitor, pyrimethamine. Plasma and urinary concentrations of candidate markers were measured using liquid chromatography-mass spectrometry. Transport activities were determined in MATE- or OCT2-expressing HEK293 cells. The deuterium-labeled compounds of candidates were administered to mice for pharmacokinetics study. Results: Urinary excretion of eleven compounds including thiamine and carnitine was significantly lower in the pyrimethamine-treatment group in humans and mice, whereas no endogenous compound was noticeably accumulated in the plasma. The renal clearance of thiamine and carnitine was decreased by 70%-84% and 90%-94% ( p < 0.05), respectively, in human. The specific uptake of thiamine was observed in MATE1-, MATE2-K- or OCT2-expressing HEK293 cells with K of 3.5 ± 1.0, 3.9 ± 0.8 and 59.9 ± 6.7 μM, respectively. The renal clearance of carnitine- d was decreased by 62% in mice treated with pyrimethamine. Conclusions: Our findings indicate that MATEs account for the efflux of thiamine and perhaps carnitine as well as drugs into the urine. The urinary excretion of thiamine is useful to detect drug interaction involving MATEs in the kidney. [ABSTRACT FROM AUTHOR]

Published
2014
Full Text
View/download PDF

45. Inhibitory effect of zinc on PEPT1-mediated transport of glycylsarcosine and beta-lactam antibiotics in human intestinal cell line Caco-2.

Author

Okamura M, Terada T, Katsura T, Saito H, and Inui K

Subjects
Animals, Caco-2 Cells, Cefotiam pharmacokinetics, Ceftibuten, Cephalosporins pharmacokinetics, Cephradine pharmacokinetics, Humans, In Vitro Techniques, Oocytes metabolism, Peptide Transporter 1, Rats, Symporters metabolism, Xenopus, Anti-Bacterial Agents pharmacokinetics, Carrier Proteins metabolism, Dipeptides pharmacokinetics, Zinc pharmacology, beta-Lactams pharmacokinetics
Abstract

Purpose: The aim of this study was to examine the effects of zinc on the intestinal peptide transporters (PEPT1 and basolateral peptide transporter) and to elucidate the mechanism of the interactions., Methods: Caco-2 cells were pretreated with zinc, and the uptake studies were carried out., Results: Zinc treatment resulted in the inhibition of [14C]glycylsarcosine (Gly-Sar) uptake via PEPT1 in a concentration-dependent manner, whereas it showed moderate inhibitory effect on the basolateral peptide transporter. Zinc also inhibited the uptake of oral beta-lactam antibiotics such as ceftibuten and cephradine by PEPT1. Kinetic analysis showed that zinc treatment increased Km values without affecting Vmax values of the [14C]Gly-Sar uptake. The inhibition of [14C]Gly-Sar uptake induced by zinc was observed in the presence of an H+ gradient but not in the absence of an H+ gradient., Conclusions: These results indicate that zinc is a competitive inhibitor of PEPT1. Zinc inhibited the PEPT1 function, possibly by interacting with histidine residues of PEPT1 that are part of an H+-binding site. These findings would provide important information for clinical, physiologic, and biochemical aspects of peptide transporters.

Published
2003
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results