Effect of salt intake on bioavailability of mizoribine in healthy Japanese males.
Bioavailability of mizoribine in subjects with the concentrative nucleoside transporter 1 (CNT1, SLC28A1) 565-A/A allele is significantly lower than that in subjects with the SLC28A1 565-G/G allele. The aims of the present study were to investigate the cellular uptake of mizoribine in CNT1- and CNT2-expressing Madin-Darby canine kidney type II (MDCKII) cells, and to evaluate the effect of salt intake on bioavailability of mizoribine in healthy Japanese volunteers with SLC28A1 565-A/A and -G/A alleles. Eight healthy males participated in the present study, and took 150 mg mizoribine concomitantly with/without 300 mg salt. Bioavailability of mizoribine was estimated by total cumulative urinary excretion of the drug. Mizoribine was taken up Na(+)-dependently into not only CNT1-expressing but also CNT2-expressing MDCKII cells, indicating that mizoribine is a substrate for both CNT1 and CNT2. Mean bioavailability of mizoribine taken with salt (83.8%) was significantly higher than that taken without salt (73.0%). These findings suggest that the salt intake is expected to improve the bioavailability of mizoribine in patients with insufficient intestinal absorption.
Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Kazuya
K
Ishida
Miki
M
Fukao
Hitomi
H
Watanabe
Masato
M
Taguchi
Toshio
T
Miyawaki
Hiroyoshi
H
Matsukura
Osamu
O
Uemura
Zufei
Z
Zhang
Jashvant D
JD
Unadkat
Yukiya
Y
Hashimoto
D000328:Adult; D000818:Animals; D001682:Biological Availability; D002478:Cells, Cultured; D003562:Cytidine / Q000493:pharmacokinetics; D004285:Dogs; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D007288:Inosine / Q000493:pharmacokinetics; D008297:Male; D026901:Membrane Transport Proteins / Q000502:physiology; D012263:Ribonucleosides / Q000493:pharmacokinetics*; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*
D007166:Immunosuppressive Agents; D026901:Membrane Transport Proteins; D012263:Ribonucleosides; D017673:Sodium Chloride, Dietary; C065171:cif nucleoside transporter; C010052:mizoribine; D007288:Inosine; D003562:Cytidine