Side effects
Toxicity may include interstitial pulmonary fibrosis ("busulfan lung"), hyperpigmentation, seizures, hepatic (veno-occlusive disease) (VOD) or sinusoidal obstruction syndrome (SOS), emesis, and wasting syndrome. Busulfan also induces thrombocytopenia, a condition of lowered blood platelet count and activity, and sometimes medullary aplasia. Seizures and VOD are serious concerns with busulfan therapy and prophylaxis is often utilized to avoid these effects. Hepatic VOD is a dose-limiting toxicity. Symptoms of VOD include weight gain, elevated bilirubin, painful hepatomegaly, and edema. The reason busulfan causes VOD is mostly unknown and can be deadly. 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.Busulfan is listed by the IARC as a Group 1 carcinogen. Dosing, administration, and pharmacokinetics
As an adjunct therapy with cyclophosphamide for conditioning prior to bone marrow transplantation in adults and children >12 kg, intravenous (IV) busulfan (Bulsulfex) is dosed at 0.8 mg/kg every six hours for 16 doses (four days). IV busulfan is usually administered over two hours. Both IV and oral formulations require prophylactic antiemetic agents administered prior to the busulfan dose and scheduled antiemetics administered thereafter. Oral bioavailability of busulfan shows a large interindividual variation. Taking busulfan on an empty stomach is recommended to reduce the risk of nausea and emesis. Peak plasma concentrations are achieved within one hour of oral administration.
Because the intrastrand DNA crosslinks cannot be repaired by cellular machinery, the cell undergoes apoptosis. Complexation
The molecular recognition of ureido-cyclodextrin with busulfan was investigated. 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. References
External links
"Busulfan". Drug Information Portal. U.S. National Library of Medicine.