Increased Access to OATP2B1 Drug Transporter Studies
Evaluating drug transporters during the drug development process is of critical importance because they assist in the movement of drugs into or out of cells and can therefore be heavily involved in drug-drug interactions (DDI). Accordingly, regulatory agencies including the FDA, EMA and PMDA have published guidance recommending evaluation of various transporters for potential drug interactions. Although they do not specifically mention the organic anion transporting polypeptide 2B1 (OATP2B1), published research has noted its likely relevance due to its high concentration in the liver and intestine [1] and similarities with OATP1B1 and OATP1B3, which are recommended for evaluation.
Expression of OATP2B1 has been documented in a wide variety of tissue, including those of predominant concern for drug developers – the liver, intestines, kidneys and blood-brain barrier – suggesting a potentially broad role in ADME, DDI, and toxicology. OATP2B1 is most likely involved in oral drug absorption of its substrate due to its intestinal expression, as well as possible local distribution processes like transfer across the blood–brain-barrier or placenta [2]. However, its physiological and pharmacological role and clinical relevance is not fully understood.
Although OATP1B1 and OATP1B3 are the primary OATPs identified for their involvement in DDI, hepatic OATP2B1 has been shown to mediate various xenobiotics, such as bromosulfophthalein (BSP), benzylpenicillin, fexofenadine, glibenclamide, pravastatin, atorvastatin, rosuvastatin, and fluvastatin [3, 4, 5, 6, 7, 8, 9], and might have a role in the absorption and disposition of a range of xenobiotics.
To help researchers more easily investigate OATP2B1, XenoTech is now offering Drug Transporter Inhibition Potential and Substrate Potential studies at its Kansas City, KS headquarters.
Learn more about in vitro drug transporter services to support preclinical drug development, view our relevant scientific resources, or contact us with any questions or to place a study.
1. McFeely, S., et al., Organic anion transporting polypeptide 2B1 – More than a glass-full of drug interactions. Pharmacol. Ther, 2019. 196(4): p. 204-215.
2. Kinzi, J., et al., OATP2B1 – The underrated member of the organic anion transporting polypeptide family of drug transporters? Biochem. Pharmacol, 2021. 188(6): article 114534.
3. Tamai, I., et al., Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochem Biophys Res Commun, 2000. 273(1): p. 251-260.
4. Noe, J., et al., Substrate-dependent drug-drug interactions between gemfibrozil, fluvastatin and other organic anion-transporting peptide (OATP) substrates on OATP1B1, OATP2B1, and OATP1B3. Drug Metab Dispos, 2007. 35(8): p. 1308-1314.
5. Nozawa, T., et al., Involvement of organic anion transporting polypeptides in the transport of troglitazone sulfate: implications for understanding troglitazone hepatotoxicity. Drug Metab Dispos, 2004. 32(3): p. 291-294.
6. Kobayashi, D., et al., Involvement of human organic anion transporting polypeptide OATP-B (SLC21A9) in pH-dependent transport across intestinal apical membrane. J Pharmacol Exp Ther, 2003. 306(2): p. 703-708.
7. Satoh, H., et al., Citrus juices inhibit the function of human organic anion-transporting polypeptide OATP-B. Drug Metab Dispos, 2005. 33(4): p. 518-523.
8. Ho, R.H., et al., Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Gastroenterology, 2006. 130(6): p. 1793-1806. 9. Miura, M., et al., Influence of SLCO1B1, 1B3, 2B1 and ABCC2 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients. Eur J Clin Pharmacol, 2007. 63(12): p. 1161-1169.