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...

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Published in:DRUG METABOLISM AND PHARMACOKINETICS 2013, Vol.28 (1), p.75-80
Main Authors: Ishida, Kazuya, Fukao, Miki, Watanabe, Hitomi, Taguchi, Masato, Miyawaki, Toshio, Matsukura, Hiroyoshi, Uemura, Osamu, Zhang, Zufei, Unadkat, Jashvant D., Hashimoto, Yukiya
Format: Article
Language:English
Subjects:
Adult
Animals
bioavailability
Biological Availability
Cells, Cultured
CNT1
CNT2
Cytidine - pharmacokinetics
Dogs
Humans
Immunosuppressive Agents - pharmacokinetics
Inosine - pharmacokinetics
Male
Membrane Transport Proteins - physiology
mizoribine
nucleoside transporters
Ribonucleosides - pharmacokinetics
salt intake
Sodium Chloride, Dietary - administration & dosage
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Summary: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.
ISSN:1347-4367
1880-0920
DOI:10.2133/dmpk.DMPK-12-NT-043