Overlapping functions of ABC transporters in topotecan disposition as determined in gene knockout mouse models.

ABSTRACT: It is established that efflux transporters of the ATP-binding cassette (ABC) superfamily can affect the pharmacokinetics of drugs through mechanisms pertaining to drug absorption, elimination, and distribution. To characterize the role of multiple transporters in topotecan's pharmacokinetics, total (lactone+carboxylate) and lactone forms were measured by liquid chromatography/tandem mass spectrometry (LC/MS-MS) in plasma, bile, urine, and feces following intravenous administration at doses of 1 and 4 mg/kg to eight mouse strains: C57BL/6 [wild-type (WT)], Abcb1(-/-), Abcc2(-/-), Abcc4(-/-), Abcg2(-/-), Abcc2;Abcb1(-/-), Abcc2;Abcg2(-/-), and Abcc4;Abcg2(-/-). Compared with WT mice and at both dose levels, the plasma areas under the curve for topotecan lactone were not significantly differe

SUBMITTER: Tiwari AK 

PROVIDER: S-EPMC3707957 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature