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HelpMayo Test ID BUAUC Busulfan, Intravenous Dose, Area Under the Curve, Plasma
Necessary Information
The time the drug administration is started and completed, the patient's dose (mg every 6 hours), body weight (kg), and age (years) must be submitted with the specimens. Without infusion start time, exact time of specimen collection, dose, and body weight, the area under the curve and clearance cannot be calculated. Age is required for assessment of the correct dose per body weight.
A completed Busulfan Information: Mail-In Specimen Instructions (T559) is required.
Specimen Required
Four plasma specimens with different collection times (keep all specimens under 1 order) are required.
Collection Container/Tube: Green top (sodium heparin) (Plasma gel/PST are not acceptable)
Submission Container/Tube: Plastic vials
Specimen Volume: 1 mL
Collection Instructions:
1. The first specimen should be collected immediately after completion of the first intravenous infusion of 0.8 mg/kg busulfan.
2. Additional specimens should also be collected at 1 hour, 2 hours, and 4 hours after completion of infusion.
3. Label each specimen with exact time of collection.
4. Busulfan degrades quickly at ambient temperature. Specimens must be kept in wet ice slurry or refrigerated at 4° C. Specimens must be centrifuged within 2 hours after collection. Separate the plasma and transfer to individual 5-mL plastic vials, labeled with exact time of collection. Immediately freeze at -20° C.
Additional Information:
This test should only be ordered when the following criteria are met:
-Busulfan dosing protocol must be intravenous administration of 0.8 mg/kg doses every 6 hours over 4 days, for a total of 16 doses
Specimens must be collected as described below:
-1 specimen collected immediately after completion of the first 2-hour IV infusion of busulfan
-1 specimen collected 1 hour after the infusion is completed
-1 specimen collected 2 hours after the infusion is completed
-1 specimen collected 4 hours after the infusion is completed and prior to the next infusion of busulfan
Useful For
Guiding dosage adjustments to achieve complete bone marrow ablation while minimizing dose-dependent toxicity
Profile Information
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| DOSE | Busulfan, IV Dose, AUC, P | No | Yes |
| BU2H | Busulfan, Immediate Post Infusion | No | Yes |
| BU3H | Busulfan, 1hr Post Infusion | No | Yes |
| BU4H | Busulfan, 2hr Post Infusion | No | Yes |
| BU6H | Busulfan, 4hr Post Infusion | No | Yes |
Special Instructions
Method Name
Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)
Reporting Name
Busulfan, IV Dose, AUC, PSpecimen Type
Plasma Na HeparinSpecimen Minimum Volume
0.25 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Plasma Na Heparin | Frozen (preferred) | 28 days | |
| Refrigerated | 72 hours |
Reject Due To
| Gross hemolysis | OK |
| Gross lipemia | OK |
| Gross icterus | OK |
Clinical Information
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 a pharmacokinetic (PK) evaluation of the area under the curve 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
AREA UNDER THE CURVE
900-1500 (mcmol/L)(min)
CLEARANCE
2.1-3.5 (mL/minute)/kg
Interpretation
Results of the timed collections 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 evaluation of IV busulfan is 1100 (mcmol/L)(min).
Area under the curve results greater than 1500 (mcmol/L)(min) are associated with hepatic veno-occlusive disease. A dose reduction should be considered before the next busulfan infusion.
Area under the curve 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 kidney 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
Failure to provide the 4 plasma specimens as described will invalidate the area under the curve calculations.
Clinical Reference
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;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 Transplant. 1995;16(1):31-42
3. Slattery JT, Risler LJ. Therapeutic monitoring of busulfan in hematopoietic stem cell transplantation. Ther Drug Monit. 1998;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;24(9):1015-1019
5. Vassal G, Re M, Gouyette A. Gas chromatographic-mass spectrometric assay for busulfan in biological fluids using a deuterated internal standard. J Chromatogr. 1988;428(2):357-361
6. Baselt RC. Disposition of Toxic Drugs and Chemicals in Man. 12th ed. Biomedical Publications; 2020
7. Busulfex. Package insert. Otsuka Pharmaceutical Co, Ltd; Updated January 2015. Accessed October 8, 2024. Available at www.accessdata.fda.gov/drugsatfda_docs/label/2015/020954s014lbl.pdf
8. Palmer J, McCune JS, Perales MA, et al. Personalizing busulfan-based conditioning: considerations from the American Society for Blood and Marrow Transplantation Practice Guidelines Committee. Biol Blood Marrow Transplant. 2016;22(11):1915-1925
Method Description
Busulfan analysis is performed by liquid chromatography tandem mass spectrometry with calculation of area under the curve (AUC) by integration of the time versus concentration curve from start of infusion to last specimen collection (6-hour AUC).(Unpublished Mayo method)
The AUC and clearance are calculated after quantification of busulfan concentration in plasma samples collected at specific time points after the initial infusion.
The AUC is calculated by integration of the plot of time in minutes from the start of infusion until the last specimen collection (independent variable), with busulfan concentration in mcmol/L (dependent variable) and straight-line extrapolation of the immediate postinfusion busulfan concentration to time zero. Clearance is calculated as the dose divided by AUC.
The recommended optimal dose is calculated based on the assumption of an ideal AUC=1100 mcmol*min.(Slattery JT, Risler LJ. Therapeutic monitoring of busulfan in hematopoietic stem cell transplantation. Ther Drug Monit. 1998;20[5]:543-549)
Day(s) Performed
Monday through Saturday
Report Available
Same day/1 to 3 daysSpecimen Retention Time
14 daysPerforming Laboratory
Mayo Clinic Laboratories in Rochester
Test Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
80299 x 4
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| BUAUC | Busulfan, IV Dose, AUC, P | 93478-6 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| DRDT2 | Draw Date | 33882-2 |
| DRDT3 | Draw Date | 33882-2 |
| DRDT4 | Draw Date | 33882-2 |
| DRDT6 | Draw Date | 33882-2 |
| DSE | Initial Dose | 93477-8 |
| DAT16 | Infusion Start Date | 88063-3 |
| DRTM6 | Draw Time | 49049-0 |
| DRTM4 | Draw Time | 49049-0 |
| DRTM3 | Draw Time | 49049-0 |
| DRTM2 | Draw Time | 49049-0 |
| 24221 | Busulfan result | 93436-4 |
| 24222 | Busulfan result | 93435-6 |
| 24223 | Busulfan result | 93434-9 |
| 24224 | Busulfan result | 93433-1 |
| TM82 | Infusion Start Time | 88060-9 |
| DAT17 | Infusion Stop Date | 88062-5 |
| TM65 | Infusion Stop Time | 88061-7 |
| W8 | Weight | 29463-7 |
| 24220 | Age | 30525-0 |
| 24225 | Area Under the Curve, (0-6 Hour) | 93476-0 |
| 24226 | Clearance | 93475-2 |
| 24227 | Recommended Dose | 93477-8 |