Busulfan, Intravenous Dose, Area Under the Curve (AUC), Plasma
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Guiding dosage adjustments to achieve complete bone marrow ablation while minimizing dose-dependent toxicity
Profile Information A profile is a group of laboratory tests that are ordered and performed together under a single Mayo Test ID. Profile information lists the test performed, inclusive of the test fee, when a profile is ordered and includes reporting names and individual availability.
|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 and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Gas Chromatography-Mass Spectrometry (GC-MS)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Busulfan, IV Dose, AUC, P
Specimen Type Describes the specimen type needed for testing
Plasma Na Heparin
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Four plasma specimens with different draw times (keep all specimens under 1 order) are required.
Collection Container/Tube: Green top (sodium heparin)
Submission Container/Tube: Plastic vials
Specimen Volume: 1 mL
1. The first specimen should be drawn immediately after termination of intravenous infusion of 0.8 mg/kg busulfan.
2. Additional specimens should also be drawn at 1 hour, 2 hours, and 4 hours after termination of infusion.
3. Label each specimen appropriately (exact time of draw).
Forms: Busulfan Information Sheet (Supply T599) in Special Instructions
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Mild OK; Gross reject
Mild OK; Gross reject
Mild OK; Gross reject
Serum gel tube
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|Plasma Na Heparin||Frozen (preferred)||7 days|
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 before hematopoietic stem cell transplant.(1) Busulfan is typically administered in intravenous (IV) doses of 0.8 mg/kg once every 6 hours over 4 days, a total of 16 doses. Dose-limiting toxicity of busulfan is hepatic veno-occlusive disease. 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.
AREA UNDER THE CURVE
This test should only be ordered when the following criteria are met:
-Busulfan dosing protocol must be intravenous (IV) administration of 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, please contact the Laboratory Director.
The optimal result for AUC (6 hour) derived from this pharmacokinetic (PK) evaluation of IV busulfan is 1,100 mcmol*min.
AUC results >1,500 mcmol*min are associated with hepatic veno-occlusive disease. A dose reduction should be considered before the next busulfan infusion.
AUC results <900 mcmol*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 <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. The time the drug administration is started and terminated, the patient's dose (mg every 6 hr), body weight (kg), and age (years) must be submitted with the specimens. Without infusion start time, exact time of specimen draw, 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.
Clinical Reference Provides recommendations for further 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
Method Description Describes how the test is performed and provides a method-specific reference
Busulfan analysis is performed by gas chromatography-mass spectrometry (GC-MS), with calculation of area under the curve (AUC) by integration of the time versus concentration curve from start of infusion to last sample collection (6-hour AUC).
AUC and clearance are calculated after quantification of busulfan concentration in blood plasma samples:
-1 sample drawn immediately after termination of a 2-hour intravenous (IV) infusion of 0.8 mg/kg busulfan
-1 sample drawn 1 hour after the infusion is terminated
-1 sample drawn 2 hours after the infusion is terminated
-1 sample drawn 4 hours after the infusion is terminated
The AUC is calculated by integration of the plot of time in minutes from the start of infusion until the last sample collection (independent variable), with busulfan concentration in umol/L (dependent variable), and with 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 umol*min. (Slattery JT, Risler LJ: Therapeutic monitoring of busulfan in hematopoietic stem cell transplantation. Ther Drug Monit 1998 October;20:543-549)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday through Saturday; 2 p.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Same day/1 day
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
80299 x 4
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|DSE||Initial Dose||In Process|
|DAT16||Infusion Start Date||N/A|
|24222||Busulfan result||In Process|
|24223||Busulfan result||In Process|
|24224||Busulfan result||In Process|
|TM82||Infusion Start Time||In Process|
|DAT17||Infusion Stop Date||In Process|
|TM65||Infusion Stop Time||In Process|
|24225||Area Under the Curve, (0-6 Hour)||In Process|
|24227||Recommended Dose||In Process|