Mablin - General Information
An alkylating agent having a selective immunosuppressive effect on bone marrow. It has been used in the palliative treatment of chronic myeloid leukemia (myeloid leukemia, chronic), but although symptomatic relief is provided, no permanent remission is brought about. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), busulfan is listed as a known carcinogen. [PubChem]
Pharmacology of Mablin
Mablin is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death.
Mablin for patients
The increased risk of a second malignancy should be explained to the patient.
Itraconazole decreases busulfan clearance by up to 25%, and may produce AUCs > 1500 µM·min in some patients. Fluconazole, and the 5-HT3 antiemetics odansetron (Zofran) and granisetron (Kytril) have all been used with BUSULFEX.
Phenytoin increases the clearance of busulfan by 15% or more, possibly due to the induction of glutathione-S-transferase. Since the pharmacokinetics of BUSULFEX were studied in patients treated with phenytoin, the clearance of BUSULFEX at the recommended dose may be lower and exposure (AUC) higher in patients not treated with phenytoin. Because busulfan is eliminated from the body via conjugation with glutathione, use of acetaminophen prior to (<72 hours) or concurrent with BUSULFEX may result in reduced busulfan clearance based upon the known property of acetaminophen to decrease glutathione levels in the blood and tissues.
BUSULFEX is contraindicated in patients with a history of hypersensitivity to any of its components.
Additional information about Mablin
Mablin Indication: For use in combination with cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous leukemia.
Mechanism Of Action: Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations.
Drug Interactions: Metronidazole Metronidazole increases the effect/toxicity of busulfan
Food Interactions: Take without regard to meals.
Generic Name: Busulfan
Synonyms: Butanedioldimethanesulfonate; Busulphan; Busulphane; Buzulfan; Sulfabutin; Sulphabutin; Tetramethylene Dimethane Sulfonate; Tetramethylenester Kyseliny Methansulfonove
Drug Category: Antineoplastic Agents; Immunosuppressive Agents; Alkylating Agents
Drug Type: Small Molecule; Approved
Absorption: Completely absorbed from the gastrointestinal tract.
Toxicity (Overdose): Signs of overdose include allergic reaction, unusual bleeding or bruising, sudden weakness or unusual fatigue, persistent cough, congestion, or shortness of breath; flank, stomach or joint pain; pronounced nausea, vomiting, diarrhea, dizziness, confusion, or darkening of the skin, chills, fever, collapse, and loss of consciousness.
Protein Binding: 32.4%
Biotransformation: Mainly Hepatic. Busulfan is predominantly metabolized by conjugation with glutathione, both spontaneously and by glutathione S-transferase (GST) catalysis.
Half Life: 2.5 hours
Dosage Forms of Mablin: Solution Intravenous
Chemical IUPAC Name: 4-methylsulfonyloxybutyl methanesulfonate
Chemical Formula: C6H14O6S2
Busulfan on Wikipedia: https://en.wikipedia.org/wiki/Busulfan
Organisms Affected: Humans and other mammals