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Impact of CYP3A4*22 on Pazopanib Pharmacokinetics in Cancer Patients.


ABSTRACT: BACKGROUND AND OBJECTIVE:As pazopanib plasma trough concentrations are correlated with treatment outcome, we explored whether single nucleotide polymorphisms in the elimination pathway of pazopanib affect systemic pazopanib concentrations. METHODS:The decreased function alleles CYP3A4 15389 C?>?T (*22), ABCB1 3435 C?>T, ABCG2 421 C?>A, and ABCG2 34G?>A were analyzed within a recently developed population-pharmacokinetic model. RESULTS:Incorporation of CYP3A4*22 in the model resulted in a 35% lower clearance for variant carriers (0.18 vs. 0.27 L/h; difference in objective function value: - 9.7; p?

SUBMITTER: Bins S 

PROVIDER: S-EPMC6451710 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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<h4>Background and objective</h4>As pazopanib plasma trough concentrations are correlated with treatment outcome, we explored whether single nucleotide polymorphisms in the elimination pathway of pazopanib affect systemic pazopanib concentrations.<h4>Methods</h4>The decreased function alleles CYP3A4 15389 C > T (*22), ABCB1 3435 C >T, ABCG2 421 C >A, and ABCG2 34G >A were analyzed within a recently developed population-pharmacokinetic model.<h4>Results</h4>Incorporation of CYP3A4*22 in the model  ...[more]

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