title: Environmental and genetic factors affecting transport of imatinib by OATP1A2.
abstract: 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.
authors.affiliation: Department of Medical Oncology, Daniel den Hoed Cancer Center, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Eechoute
authors.forename: R M
authors.initials: RM
authors.lastname: Franke
authors.forename: W J
authors.initials: WJ
authors.lastname: Loos
authors.forename: L A
authors.initials: LA
authors.lastname: Scherkenbach
authors.forename: I
authors.initials: I
authors.lastname: Boere
authors.forename: J
authors.initials: J
authors.lastname: Verweij
authors.forename: H
authors.initials: H
authors.lastname: Gurney
authors.forename: R B
authors.initials: RB
authors.lastname: Kim
authors.forename: R G
authors.initials: RG
authors.lastname: Tirona
authors.forename: R H J
authors.initials: RH
authors.lastname: Mathijssen
authors.forename: A
authors.initials: A
authors.lastname: Sparreboom
mesh_terms: D000818:Animals; D001549:Benzamides; D001693:Biological Transport, Active / Q000502:physiology; D004777:Environment; D005260:Female; D006367:HeLa Cells; D006801:Humans; D000068877:Imatinib Mesylate; D027361:Organic Anion Transporters / Q000235:genetics* / Q000378:metabolism*; D010879:Piperazines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011743:Pyrimidines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D001549:Benzamides; D027361:Organic Anion Transporters; D010879:Piperazines; D011743:Pyrimidines; C512988:SLCO1A2 protein, human; D000068877:Imatinib Mesylate