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2043 Background: Increased oral clearance (CL/F) of drugs that are CYP3A and/or P-glycoprotein (P-gp) substrates has been reported in African-American (AA) compared to Caucasian (C) patients (pts). The primary study objective was to test the hypothesis that the pharmacokinetics and pharmacodynamics of DCTX, an intravenously administered substrate for CYP3A and P-gp, would be different between C and AA pts. Methods: DCTX population pharmacokinetics and pharmacodynamics were studied following a single intravenous dose of DCTX (75 or 100 mg/m2) in cancer pts. of C and AA ethnicity. Timed blood samples, using a published limited sampling regimen, were obtained. Clinical toxicity and absolute neutrophil count (ANC) were monitored on days 8, 15 and 22 post treatment. DCTX concentrations were measured by HPLC. A complete population pharmacokinetic analysis is being performed and genotyping for CYP3A and P-gp is ongoing using sequencing or polymerase chain reaction -restriction fragment length polymorphisms (PCR-RFLP). Results: 109 pts were enrolled into the study. There were 69 C (43M:26F) median age 61 yr (range 29–73) and 40 AA (26M:14F) median age 63 yr (range 38–81). Mean ± SD DCTX Cmax and C6h (all adjusted to 75 mg/m2dose) are shown in the table below. There was no difference in the percent reduction in ANC from baseline (mean ± SD; n) between C (81± 19%; n=43) and AA (75± 24%; n=20) when patients who received 75 mg/m2 DCTX were compared. Relationships between DCTX pharmacokinetics and CYP3A and P-gp genotype in the two ethninc groups are being explored. Conclusions: There was no apparent difference in DCTX pharmacokinetics or DCTX induced myelosuppression between cancer patients of either C or AA ethnicity. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis
Lewis et al. (Thu,) studied this question.