Hiroyuki Kusuhara

A cDNA encoding the new member of the multispecific organic anion transporter family, OAT3, was isolated by the reverse transcription-polymerase chain reaction cloning method. Degenerate primers were designed based on the sequences conserved among OAT1, OAT2, and organic cation transporter 1 (OCT1), and reverse transcription-polymerase chain reaction was performed using rat brain poly(A)+ RNA. The 536-amino acid protein sequence encoded by OAT3 showed 49, 39, and 36% identity to those of OAT1, O

Transporters govern drug movement into and out of tissues, thereby playing an important role in drug disposition in plasma and to the site of action. The molecular cloning of such transporters has clarified the importance of members of the solute carrier family, such as OATP/SLCO, OCT/SLC22, OAT/SLC22, and MATE/SLC47, and the ATP-binding cassette transporters, such as P-glycoprotein/ABCB1, MRPs/ABCC, and BCRP/ABCG2. Elucidation of molecular characteristics of transporters has allowed the identif

A microdose study of metformin was conducted to investigate the predictability of drug-drug interactions at the therapeutic dose (ThD). Healthy subjects received a microdose (100 µg) or ThD (250 mg) of metformin orally, with or without a potent and competitive multidrug and toxin extrusion (MATE) inhibitor, pyrimethamine (50 mg, p.o.), in a crossover fashion. Pyrimethamine significantly reduced the renal clearance of metformin by 23 and 35% at the microdose and ThD, respectively. At ThD, but not

BACKGROUND AND PURPOSE An ATP-binding cassette (ABC) transporter, breast cancer resistance protein (BCRP)/ABCG2, limits oral bioavailability of sulphasalazine. Here we examined the effect of curcumin, the principal curcuminoid of turmeric, on oral bioavailability of microdoses and therapeutic doses of sulphasalazine in humans. EXPERIMENTAL APPROACH Effects of curcumin were measured on the ATP-dependent sulphasalazine uptake by hBCRP-expressing membrane vesicles and on oral bioavailability of sul