TRANSPLANTATION 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 F .05) determinants of CL/F by linear regression were: actual body weight (BW; r2 5 0.300), body surface area (BSA; r2 5 0.277), adjusted ideal body weight (AIBW; r2 5 0.265), and ideal body weight (IBW; r2 5 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/m2) was 16.2% lower (P F .001) than for obese patients (BMI, 27 to 35 kg/m2). 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 6 24 v 110 6 24 mL/min/m2, P 5 1.0) or AIBW (3.04 6 0.65 v 3.19 6 0.67 mL/min/kg, P 5 .597) were similar in normal and obese patients. Non-Hodgkin’s lymphoma patients (n 5 10) had approximately 32% lower mean busulfan CL/F expressed relative to BW, BSA, or AIBW compared with patients with chronic myelogenous leukemia (n 5 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. r 1999 by The American Society of Hematology.