Busulfan

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Busulfan
Clinical data
Trade namesMyleran, Busilvex, Busulfex IV
Other names1,4-butanediol dimethanesulfonate
AHFS/Drugs.comMonograph
MedlinePlusa682248
License data
Pregnancy
category
  • AU: D
Routes of
administration		By mouth, intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability60–80% (oral)
Protein binding32.4%
MetabolismLiver
Elimination half-life2.5 hours
ExcretionUrine (25–60%)
Identifiers
  • Butane-1,4-diyl dimethanesulfonate
JSmol)
  • CS(=O)(=O)OCCCCOS(=O)(=O)C
  • InChI=1S/C6H14O6S2/c1-13(7,8)11-5-3-4-6-12-14(2,9)10/h3-6H2,1-2H3 checkY
  • Key:COVZYZSDYWQREU-UHFFFAOYSA-N checkY
  (verify)

Busulfan (Myleran,

alkyl sulfonates
. Its chemical designation is 1,4-butanediol dimethanesulfonate.

History

Busulfan was approved by the US

chronic myeloid leukemia (CML) in 1999. Busulfan was the mainstay of the chemotherapeutic treatment of chronic myeloid leukemia (CML) until it was displaced by the new gold standard, imatinib
, though it is still in use to a degree as a result of the drug's relative low cost.

Indications

Busulfan is used in pediatrics and adults in combination with

myeloproliferative disorders
. Busulfan can control tumor burden but cannot prevent transformation or correct cytogenic abnormalities.

The drug was recently used in a study to examine the role of platelet-transported serotonin in liver regeneration.[2]

Availability

Myleran is supplied in white film coated tablets with 2 mg of busulfan per tablet. After 2002, a great interest has appeared for intravenous presentations of busulfan. Busulfex is supplied as an intravenous solution with 6 mg/ml busulfan. Busulfex has proved equally effective as oral busulfan, with presumedly less toxic side effects. Pharmacokinetic and dynamic studies support this use, that has prompted its usage in transplantation regimes, particularly in frail patients. Fludarabine + busulfan is a typical example of this use.

Side effects

Toxicity may include interstitial

Ursodiol
may be considered for prophylaxis of veno-occlusive disease.

Antiemetics are often administered prior to busulfan to prevent vomiting (emesis).

Phenytoin may be used concurrently to prevent the seizures. Levetiracetam, has shown efficacy for the prophylaxis against busulfan-induced seizures. Benzodiazepines can also be used for busulfan-induced seizures.[6]

Busulfan is listed by the IARC as a Group 1 carcinogen.

Dosing, administration, and pharmacokinetics

As an adjunct therapy with

emesis
.

Peak plasma concentrations are achieved within one hour of oral administration. About 30% of the drug is bound to plasma proteins, such as albumin.

Busulfan

first order kinetics
, such that the adjusted dose = current dose × (target AUC/actual AUC).

Drug interactions

Busulfan is metabolized via

acetaminophen is also metabolized via glutathione and may deplete stores. Phenytoin increases hepatic clearance of busulfan (resulting in decreased busulfan AUC). However, clinical studies of busulfan were completed with patients taking phenytoin, so no empiric dose adjustment is necessary if patients are taking phenytoin
with busulfan.

Pharmacology

Busulfan is an

DNA crosslinking prevents DNA replication. Because the intrastrand DNA crosslinks cannot be repaired by cellular machinery, the cell undergoes apoptosis.[9]

Complexation

The molecular recognition of ureido-cyclodextrin with busulfan was investigated.[10] The formation of complexes was observed with electrostatic interactions between urea and the sulfonate part of busulfan.

Another structure was used for this complexation type, two disaccharidyl units connected by urea linkers to a diazacrown ether organizing platform.[11]

References

  1. FDA
    . Retrieved 22 Oct 2023.
  2. S2CID 43189753
    .
  3. PMID 8932850
    .
  4. ^
    PMID 15571949
    .
  5. PMID 13489262
    .
  6. S2CID 31338996
    .
  7. PMID 7919328
    . Retrieved 2018-02-04.
  8. S2CID 28337537
    .
  9. ^ Karstens A, Kramer I (2007). "Chemical and physical stability of diluted busulfan infusion solutions". EJHP Science. 13: 40–7.
  10. doi:10.1016/j.tet.2006.10.070
    .
  11. doi:10.1016/j.tet.2009.05.057
    .

External links

  • "Busulfan". Drug Information Portal. U.S. National Library of Medicine.
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