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 b y linear regression were: actual body weight (BW; r(2) = 0.300), body surfa ce 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 relati ve 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% lo wer 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 bod y size or disease does not diminish Interpatient variability sufficiently t o obviate plasma level monitoring in many indications. (C) 1999 by The Amer ican Society of Hematology.