Impact of obesity on doxorubicin pharmacokinetics in women with breast cancer

Introduction Experts suggest doxorubicin clearance is decreased in women with a body mass index (BMI) of ≥35 kg/m 2 . However, few data support this recommendation. Methods Women receiving doxorubicin for breast cancer in three BMI groups were recruited (n = 15). Doxorubicin dosing was determined by body surface area and was administered by 30-min intravenous infusion. Blood samples were obtained at 0 h (pre-dose) and 0.5, 1, 1.5, 2, 3, 4, 5, 12–24, and 24–72 h following the beginning of infusion. Concentrations of doxorubicin and its metabolite, doxorubicinol, were assayed by LC-MS/MS. Non-compartment analysis was done using PKanalix2021R2 for pharmacokinetic (PK) analyses. Results The median [range] BMI and age were 30.3 [23.5–57] kg/m 2 and 53 [31–69] years. Thirteen of the 15 women had samples available for analysis. Four of the 13 had a BMI ≥ 35.0 kg/m 2 . PK parameters ranged from 37.8% (AUC 0−inf ) to 91.0% (Vd). Doxorubicinol PK parameters ranged from 37.8% (C max ) to 67.6% (AUC 0−inf ). The average doxorubicinol:doxorubicin AUC lasts ratio was 0.26 (range: 0.04–0.88). A t-test didn’t suggest a significant difference in individual PK parameters (BMI < 35 kg/m 2 vs. ≥35.0 kg/m 2 ). The two highest clearances (380 L/h and 250 L/h) had a BMI ≥ 35.0 kg/m 2 ; also, the highest clearance (1114 L/h) for doxorubicinol was ≥35.0 kg/m 2 . Conclusions Large interindividual variabilities in doxorubicin PK were observed in women up to a BMI of 57 kg/m 2 and a total body weight of 141.5 kg. Women with a BMI ≥ 35.0 kg/m 2 and breast cancer did not appear to have lower clearances of doxorubicin. ClinicalTrials.gov ID NCT01537029.