BUSULFEX: profile and news

PDL BioPharma Announces Fourth Quarter and Full Year 2005 ... Feb 27, 2006
...growing commercial presence in the acute-care hospital market with three proprietary marketed products in Cardene(R) IV, Retavase(R) and IV Busulfex(R)," said ... - PharmaLive.com (press release),

PDL BioPharma Announces Fourth Quarter and Full Year 2005 ... Feb 27, 2006
...commercial presence in the acute-care hospital market with three proprietary marketed products in Cardene® IV, Retavase® and IV Busulfex®," said Mark McDade ... - Yahoo! News (press release)

PDL's Potent Pick-Me-Up Feb 27, 2006
IV Busulfex is approved as a conditioning agent to be used in combination with cyclophosphamide prior to blood or marrow transplant in patients with chronic ... - BusinessWeek

Protein Design Labs Becomes PDL BioPharma Jan 9, 2006
...of hypertension when oral therapy is not feasible or desirable, Retavase(R) (reteplase) for acute myocardial infarction (AMI), and IV Busulfex(R) (busulfan), a ... - PR Newswire (press release),

PDL Announces Strong Second Quarter 2005 Financial Results Aug 4, 2005
...oral therapy is not feasible or desirable; Retavase, used to dissolve coronary blood clots and improve blood flow in heart attack patients; IV Busulfex(R), a ... - PR Newswire (press release)

Protein Design Labs Announces First Quarter 2005 Financial Results May 2, 2005
...for the period reflected net sales of Cardene(R) IV for the control of hypertension when oral therapy is neither feasible or desirable; IV Busulfex(R), a ... - PharmaLive.com

Protein Design Labs Announces First Quarter 2005 Financial Results May 2, 2005
...period reflected net sales of Cardene® IV for the control of hypertension when oral therapy is neither feasible or desirable; IV Busulfex®, a conditioning ... - Yahoo News

Vion Gets SPA Go-Ahead For AML Drug's Phase III Feb 10, 2005
That drug is ESP's approved Busulfex, a formulation of busulfan for a different type of leukemia - chronic myelogenous - to be used in combination with ... - BioWorld Online (subscription)

Other information

Indication
For use in combination with cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous leukemia.

Pharmacology
Busulfan 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.

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 Category
Antineoplastic Agents; Immunosuppressive Agents; Alkylating Agents; ATC:L01AB01

Brand Names/Synonyms
2041 C. B.; AN 33501; Busulfan; Busulfex; Busulphan; Busulphane; Butanedioldimethanesulfonate; Buzulfan; C.B. 2041; CB 2041; Citosulfan; G.T. 41; GT 2041; GT 41; Leucosulfan; Mablin; Mielevcin; Mielosan; Mielucin; Milecitan; Mileran; Misulban; Mitosan; Mitostan; Myeleukon; Myeloleukon; Myelosan; Myelosanum, Busulphan; Mylecytan; Myleran; Myleran Tablets; NCI-C01592; NSC 750; NSC-750; Nsc-750sulphabutin; Sulfabutin; Sulphabutin; Tetramethylene Dimethane Sulfonate; Tetramethylenester Kyseliny Methansulfonove; X 149

Dosage Forms
SOLUTION; TABLET

Absorption
Completely absorbed from the gastrointestinal tract.

Interactions
Interactions for Busulfan:

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.

Chemical IUPAC Name
1,4-bis(methylsulfonyloxy)butane

Chemical Formula
C6H14O6S2

Half Life
2.5 hours

Drug Type
Approved Drug

# Accession No
APRD00664

CAS Registry Number
55-98-1