Article ID Journal Published Year Pages File Type
2138684 Leukemia Research 2009 7 Pages PDF
Abstract

Zosuquidar is a potent and specific inhibitor of P-glycoprotein (P-gp). In preliminary experiments, blockade of P-gp for at least 12 h was required to reverse daunorubicin resistance. Because of the short half-life of zosuquidar, we performed a phase I trial of this drug as a 72-h infusion (CIV) in 16 patients during leukemic induction with daunorubicin and cytarabine. Study goals were to establish safety and determine the dose required for P-gp inhibition in NK cells and AML blasts. >90% P-gp inhibition was achieved within 2 h at a plasma threshold of 132 ng/ml zosuquidar. The recommended phase II dose of zosuquidar is 700 mg/day.

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