Blood, Vol. 93 No. 12 (June 15), 1999:
pp. 4436-4440
The Impact of Obesity and Disease on Busulfan Oral Clearance in Adults
John P. Gibbs,
Ted Gooley,
Bruce Corneau,
Georgia Murray,
Patricia Stewart,
Frederick R. Appelbaum, and
John T. Slattery
From Fred Hutchinson Cancer Research Center, Seattle WA; and
Department of Pharmaceutics, University of Washington, Seattle, WA.
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; r2 = 0.300), body surface area (BSA;
r2 = 0.277), adjusted ideal body weight (AIBW;
r2 = 0.265), and ideal body weight (IBW; r2
= 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 < .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 ± 24 v 110 ± 24 mL/min/m2, 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.
