BUAUC - Clinical: Busulfan, Intravenous Dose, Area Under the Curve (AUC), Plasma

Test Catalog

Test Name

Test ID: BUAUC    
Busulfan, Intravenous Dose, Area Under the Curve (AUC), Plasma

Useful For Suggests clinical disorders or settings where the test may be helpful

Guiding dosage adjustments to achieve complete bone marrow ablation while minimizing dose-dependent toxicity

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Busulfan is an alkylating agent used to ablate bone marrow cells prior to hematopoietic stem cell transplantation for chronic myelogenous leukemia.(1) Busulfan is typically administered intravenously (IV) at the recommended dosage of 0.8 mg/kg of actual or ideal body weight (whichever is lower) and given once every 6 hours over 4 days for a total of 16 doses. Dose-limiting toxicity of busulfan includes veno-occlusive liver disease, seizures, and coma. To avoid toxicity while ensuring busulfan dose adequacy to completely ablate the bone marrow, IV dosing should be guided by pharmacokinetic (PK) evaluation of area under the curve (AUC) and clearance after the first dose.(2) The PK evaluation should be carried out at the end of the first dose, with results of PK testing available to facilitate dose adjustment before beginning the fifth dose.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.


900-1,500 (mcmol/L)(min)



2.1-3.5 (mL/minute)/kg

Interpretation Provides information to assist in interpretation of the test results

This test should only be ordered when the following criteria are met:

-Busulfan dosing protocol must be intravenous (IV) administration of 0.8 mg/kg doses every 6 hours over 4 days, for a total of 16 doses

-Specimens must be drawn as described below:

 - 1 specimen drawn immediately after termination of a 2-hour IV infusion of busulfan

 - 1 specimen drawn 1 hour after the infusion is terminated

 - 1 specimen drawn 2 hours after the infusion is terminated

 - 1 specimen drawn 4 hours after the infusion is terminated


These results will be used to calculate a 6-hour area under the curve (AUC). If a different dosing or specimen collection protocol is used, or if different calculations are required, contact the Laboratory Director.


The optimal result for AUC (6 hour) derived from this pharmacokinetic (PK) evaluation of IV busulfan is 1,100 (mcmol/L)(min).


AUC results greater than 1,500 (mcmol/L)(min) are associated with hepatic veno-occlusive disease. A dose reduction should be considered before the next busulfan infusion.


AUC results below 900 (mcmol/L)(min) are consistent with incomplete bone marrow ablation. A dose increase should be considered before the next busulfan infusion.


Clearance of busulfan in patients with normal renal function is usually in the range of 2.1 to 3.5 (mL/min)/kg.


Elevated AUC is typically associated with clearance below 2.5 (mL/min)/kg, most frequently due to diminished activity of glutathione S-transferase A1-1 activity.(3)

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This assay requires 4 plasma specimens. Each specimen must be drawn at the intervals described above and labeled with the exact draw time. The specimen accession times should reflect these times.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Santos GW, Tutschka PJ, Brookmeyer R, et al: Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide. N Engl J Med 1983 December 1;309(22):1347-1353

2. Slattery JT, Sanders JE, Buckner CD, et al: Graft-rejection and toxicity following bone marrow transplantation in relation to busulfan pharmacokinetics. Bone Marrow Transpl 1995 July;16(1):31-42

3. Slattery JT, Risler LJ: Therapeutic monitoring of busulfan in hematopoietic stem cell transplantation. Ther Drug Monit 1998 October;20(5):543-549

4. Czerwinski M, Gibbs M, Slattery JT: Busulfan conjugation by glutathione S-transferases alpha, mu, and pi. Drug Metab Dispos 1996 September;24(9):1015-1019

Special Instructions and Forms Library of PDFs including pertinent information and consent forms, specimen collection and preparation information, test algorithms, and other information pertinent to test