Environmental and Genetic Factors Affecting Transport of Imatinib by OATP1A2

• Published in: Clinical pharmacology and therapeutics Vol. 89; no. 6; pp. 816 - 820
• Main Authors: Eechoute, K, Franke, RM, Loos, WJ, Scherkenbach, LA, Boere, I, Verweij, J, Gurney, H, Kim, RB, Tirona, RG, Mathijssen, RHJ, Sparreboom, A
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01-06-2011
• Subjects: Animals; Benzamides; Biological and medical sciences; Biological Transport, Active - physiology; Environment; Environment. Living conditions; Female; HeLa Cells; Humans; Imatinib Mesylate; Medical sciences; Organic Anion Transporters - genetics; Organic Anion Transporters - metabolism; Pharmacology. Drug treatments; Piperazines - antagonists & inhibitors; Piperazines - metabolism; Public health. Hygiene; Public health. Hygiene-occupational medicine; Pyrimidines - antagonists & inhibitors; Pyrimidines - metabolism; Xenopus laevis; Antineoplastic agent; Human; Imatinib; Health and environment; Enzyme; Tyrosine kinase inhibitor; Transferases; Enzyme inhibitor; Environmental factor; Transport; Protein-tyrosine kinase; Genetic determinism
• ISSN: 0009-9236; 1532-6535
• DOI: 10.1038/clpt.2011.42

The bioavailability of orally administered imatinib is >90%, although the drug is monocationic under the acidic conditions in the duodenum. In vitro, we found that imatinib is transported by the intestinal uptake carrier organic anion transporting polypeptide (OATP1A2) and that this process is sensitive to pH, rosuvastatin, and genetic variants. However, in a study in patients with cancer, imatinib absorption was not associated with OATP1A2 variants and was unaffected by rosuvastatin. These findings highlight the importance of verifying in a clinical setting the drug–transporter interactions observed in in vitro tests.
Clinical Pharmacology & Therapeutics (2011) 89 6, 816–820. doi:10.1038/clpt.2011.42