Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2138684 | Leukemia Research | 2009 | 7 Pages |
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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Authors
Jeffrey E. Lancet, Maria R. Baer, George E. Duran, Alan F. List, Robert Fielding, John F. Marcelletti, Pratik S. Multani, Branimir I. Sikic,