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; 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.
Gibbs
J P
JP
Fred Hutchinson Cancer Research Center, Seattle WA, USA.
Gooley
T
T
Corneau
B
B
Murray
G
G
Stewart
P
P
Appelbaum
F R
FR
Slattery
J T
JT
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D001830:Body Surface Area; D001835:Body Weight; D002066:Busulfan / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism; D016014:Linear Models; D008111:Liver Function Tests; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D012727:Sex Characteristics
D002066:Busulfan