OATP transporters

Pharmacogenomics of human OATP transporters. Naunyn-Schmiedehergs Archives of Pharmacology, 372, 432-443. 

Kim RB. Organic anion-transporting polypeptide (OATP) transporter family and drug disposition. Eur J Clin Invest 2003 33(suppl 2) 1-5. 

Organic anion transporter protein inhibition (OATP) - transports drugs into hepatocytes... 

Fexofenadine and digoxin are both well-known substrates for OATP transport, though the relative contribution of OATP modulation on drug interactions involving these two agents is unclear, since both are also P-gp substrates. The 60-80% reduction in fexofenadine bioavailability that results from orange, apple, and grapefruit juice consumption, however, is likely the result of OATP inhibition, rather than of P-gp induction (94). 

Inhibitors of OATP transport are typically ster-ically bulky compounds, including anions, cations, and neutral compounds (95). Various medications have been shown to interact with OATPs, including HMG CoA reductase inhibitors, cyclosporine, quinidine, rifampin, ketoconazole, verapamil, and certain protease inhibitors. Cyclosporine and rifampin have relatively high ratios of plasma concentration to Ki, suggesting the potential for clinically significant drug-drug interactions via modulation of OATP. On the other hand, plasma concentrations of pravastatin are... 

Gong IY, Rim RB (2013) Impact of genetic variation in OATP transporters to drug disposition and response. Drug Metab Pharmacokinet 28 4-18... 

OATP transporters, SLCOICI, SLC02B1, SLC03A1, SLC04A1, and SLC04C1 have been found in the jejunum, and also in the colon, with the exception of SLC03A1 [3[. OATP-B (SLC02B1) accepts bile salts, as well as pravastatin (XIII) and sulfate conjugates of steroid hormones, and is localized in the apical membrane of enterocytes [32]. 

Niemi, M. (2007) Role of OATP transporters in the disposition of drugs. Pharmacogenomics, 8, 787—802. 

Konig, J., Seithel, A., Gradhand, U. and Fromm, M.F. (2006) Pharmacogenomics of human OATP transporters. Naunyn-Schmiedebergs Archives of Pharmacology, 372, 432—443. 

The OATP Transporter Family Species and Tissue Distribution... 

Konig J, Seithel A, Gradhand U, et al. (2006). Pharmacogenomics of human OATP transporters. Naunyn-Schmiedeberg s Arch. Pharmacol. 372 432-443. 

Troglitazone sulfate (Ml, the main metabolite) undergoes biliary excretion and accounts for up to 85% of the dose in humans (Loi et al. 1999). In patients with hepatic impairment, troglitazone sulfate was found to accumulate about fourfold in plasma with a threefold increased half-life (Ott et al. 1998 Loi et al. 1999). This metabolite also inhibited the canalicular bile salt export pump (Bsep), organic anion transporting polypeptide (OATP) transporters as well as drug transporters, suggesting it contributes to the hepatotoxicity. 

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