PII‐69

AIMS The purpose of this study was to develop a population pharmacokinetic model of Genasense™ (G3139; Genta, Inc.) and its active metabolites, N‐1 and N‐2 from two primary studies in subjects with malignant melanoma (GPK101) and lymphocytic leukemia (GL208). METHODS G3139 was administered in study GPK101 (24 subjects) at an IV infusion dose of 7 mg/kg/day for 7 days and in study GL208 (40 subjects) at IV infusion doses of 3 to 7 mg/kg/day for 5 to 7 days. A population model was developed using NONMEM for GPK101 study, and the parameter estimates from this study were used as priors to fit sparse data from the GL208 study. RESULTS A 1‐compartment PK model best described the disposition of G3139 and its metabolites, N‐1 and N‐2. Weight was built into the base model and no other tested covariates (race, age, and sex) were found to be statistically significant. Population values for the clearance and volume of distribution of G3139 were estimated at 6.87 +/− 0.35 L/h and 10.5 +/− 0.54 L with an interindividual variability of 23 and 27%, respectively. The estimated clearance for its metabolites, N‐1 was 9.98 L/h (CV=2.5%), and N‐2 was 15.7 L/h (CV=1.6%). Data from GL208 study fitted reasonably well with the Bayesian estimates from the GPK101 study. CONCLUSIONS Plasma data of G3139 and its metabolites could be adequately described by the developed population model, which may be useful in predicting the time courses, including interindividual variability, after intravenous administrations of G3139. Clinical Pharmacology & Therapeutics (2005) 79 , P54–P54; doi: 10.1016/j.clpt.2005.12.194