13501 Background: Doxorubicin, a topoisomerase II inhibitor, is widely used in the management of breast cancer. The aim of the present study was to characterize the population pharmacokinetics of doxorubicin among Asian breast cancer patients and explore the influence of patient covariates on its disposition characteristics. Methods: Asian patients(N=51) receiving adjuvant chemotherapy with Adriamycin(A) and Cyclophosphamide(C) were recruited for the study. Patients received doxorubicin (range:56–61 mg/m2) as a 20 minutes intravenous infusion and blood samples were collected at 0, 0.5, 1, 4, 8 and 24hrs. Plasma concentrations were measured by HPLC. Non-linear mixed effect modeling was applied for the analysis of concentration-time profile of doxorubicin and doxorubicinol using NONMEM(6). Patient covariates such as age, weight, height, ethnicity, ER status, PR status and HER-2/neu status were included in the analysis to explain the pharmacokinetic variability of doxorubicin. Model robustness was assessed by nonparametric bootstrapping and predictive check procedures (N=1000). Results: A 5-compartment model including 3 compartments for doxorubicin and 2 compartments for doxorubicinol was found to adequately explain their pharmacokinetics. Model estimates for doxorubicin clearance(CL) was 34.7L/h. The intercompartmental clearance(Q2) between the central compartment (V1:8.24L) and peripheral compartment I (V2:444L) was 25.5L/h, and the intercompartmental clearance(Q3) between the central compartment and peripheral compartment II (V3:11.1L) was 7.26L/h. The apparent clearance of doxorubicinol(CLm) was 68.1L/h and the intercompartmental clearance(Q4) of metabolite central compartment(Vcm:483L) and its peripheral compartment(Vpm:984L) was 1970L/h. The patient covariates had no significant impact on the doxorubicin pharmacokinetic variability. Conclusions: The final allometrically scaled model showed 22.2% variability of doxorubicin clearance and 32.4% variability in the volume of distribution between the subjects. Further studies are ongoing to investigate the influence of polymorphisms in genes encoding various proteins across the doxorubicin biochemical pathway and their impact on the pharmacokinetic variability of doxorubicin. No significant financial relationships to disclose.