The impact of obesity and disease on busulfan oral clearance in adults

The apparent oral clearance (CL/F, mL/min) of busulfan was measured in 279 adolescent and adult patients. Significant (P < .05) determinants of CL/F by linear regression were: actual body weight (BW; r(2) = 0.300), body surface area (BSA; r(2) = 0.277), adjusted ideal body weight (AIBW; r(2) = 0.265), and ideal body weight (IBW; r(2) = 0.173); whereas body mass index (BMI), height, age, gender, and disease were less important predictors. CL/F (mL/min) for normal weight patients (BMI, 18 to 27 kg/m(2)) was 16.2% lower (P < .001) than for obese patients (BMI, 27 to 35 kg/m(2)). Thus, expressing CL/F relative to BW did not eliminate statistically significant differences between normal and obese patients. However, busulfan CL/F expressed relative to BSA (110 +/- 24 v 110 +/- 24 ml/min/m(2), P = 1.0) or AIBW (3.04 +/- 0.65 v 3.19 +/- 0.67 ml/min/kg, P = .597) were similar in normal and obese patients. Non-Hodgkin's lymphoma patients (n = 10) had approximately 32% lower mean busulfan CL/F expressed relative to BW, BSA, or AIBW compared with patients with chronic myelogenous leukemia (n = 73). Routine dosing on the basis of BSA or AIBW in adults and adolescents does not require a specific accommodation for the obese. However, dosing based on BSA may be improved by considering CL/F differences in certain diseases. Adjusting dose for body size or disease does not diminish Interpatient variability sufficiently to obviate plasma level monitoring in many indications. (C) 1999 by The American Society of Hematology.