Search References Drug Actions/Targets About Access data Feedback
Sign In
mitontu@gmail.com
2021 MitoTox | (CC BY-NC 4.0)
Drug

D0752 | Busulfan

Molecular Formula C6H14O6S2
Molecular Weight 246.3
Structure
State solid
Clearance * 2.52 ml/min/kg [Following an infusion of dose of 0.8 mg/kg every six hours, for a total of 16 doses over four days]
Route of elimination Following administration of 14C- labeled busulfan to humans, approximately 30% of the radioactivity was excreted into the urine over 48 hours; negligible amounts were recovered in feces. Less than 2% of the administered dose is excreted in the urine unchanged within 24 hours. Elimination of busulfan is independent of renal function.
Protein binding 32% bound to plasma proteins and 47% bound to red blood cells.
Half life 2.6 hours
Absorption Completely absorbed from the gastrointestinal tract. Busulfan is a small, highly lipophilic molecule that crosses the blood-brain-barrier. The absolute bioavailability, if a single 2 mg IV bolus injection is given to adult patients, is 80% ± 20%. In children (1.5 - 6 years old), the absolute bioavailability was 68% ± 31%. When a single oral dose is given to patients, the area under the curve (AUC) was 130 ng•hr/mL. The peak plasma concentration when given orally is 30 ng/mL (after dose normalization to 2 mg). It takes 0.9 hours to reach peak plasma concentration after dose normalization to 4 mg.

L

L01AB01 Busulfan


[L01AB] Alkyl sulfonates


[L01A] ALKYLATING AGENTS


[L01] ANTINEOPLASTIC AGENTS


[L] Antineoplastic and immunomodulating agents

Toxicity Dose Time Species Model Method Action Positive criterion Reference
MEMBRANE POTENTIAL 14.43±5.99 human qHTS-HepG2 MMP assay decrease IC50 163
MEMBRANE POTENTIAL 2 human HepG2 MMP assay decrease IC50 163
MEMBRANE POTENTIAL 6.15±3.62 rat hepatocytes MMP assay decrease IC50 163
MEMBRANE POTENTIAL 483.1 µM 30 mins mouse liver mitochondria Rh123 fluorescence (excitation 485 nm, emission 535 nm) are recorded using a fluorescence multi-well plate reader (mCICCP (20 µM) treatments was considered as the 100% baseline for ΔΨm loss) decrease EC20 36
RESPIRATION 169.8 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition. decrease EC20 36
RESPIRATION ND 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition. Negative EC20 36
SWELLING > 800 µM 30 mins mouse liver mitochondria swelling assay: Absorbance at 545 nm using a fluorescence multi-well plate reader (CaCl2 (50 µM) was considered as the 100% baseline for the swelling ) increase EC20 36

Target Dose Time Species Model Method Action Positive criterion Reference
NADH:ubiquinone reductase 169.8 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition. inhibit EC20 36
Succinate dehydrogenase ND 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition. Negative EC20 36
Cytochrome c > 400 µM 30 mins mouse liver mitochondria Cytochrome c release was evaluated using ELISA kit ( 20 µg/ml Alamethicin was used as 100% baseline) release EC20 36

Pictogram Signal Statements Precautionary Statement Codes
Danger

Aggregated GHS information provided by 50 companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.


H300 (18%): Fatal if swallowed [Danger Acute toxicity, oral]


H301 (82%): Toxic if swallowed [Danger Acute toxicity, oral]


H310 (80%): Fatal in contact with skin [Danger Acute toxicity, dermal]


H315 (18%): Causes skin irritation [Warning Skin corrosion/irritation]


H319 (18%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]


H330 (82%): Fatal if inhaled [Danger Acute toxicity, inhalation]


H335 (18%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure


Respiratory tract irritation]


H340 (16%): May cause genetic defects [Danger Germ cell mutagenicity]


H350 (100%): May cause cancer [Danger Carcinogenicity]


H360 (14%): May damage fertility or the unborn child [Danger Reproductive toxicity]


H373 (14%): Causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]


Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.


 P201, P202, P260, P261, P262, P264, P270, P271, P280, P281, P284, P301+P310, P302+P350, P302+P352, P304+P340, P305+P351+P338, P308+P313, P310, P312, P314, P320, P321, P322, P330, P332+P313, P337+P313, P361, P362, P363, P403+P233, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)
Danger

H301: Toxic if swallowed [Danger Acute toxicity, oral]


H340: May cause genetic defects [Danger Germ cell mutagenicity]


H350: May cause cancer [Danger Carcinogenicity]


H360: May damage fertility or the unborn child [Danger Reproductive toxicity]


H371: May cause damage to organs [Warning Specific target organ toxicity, single exposure]


H373: Causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]


 P201, P202, P260, P264, P270, P281, P301+P310, P308+P313, P309+P311, P314, P321, P330, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)

Organism Test type Route Dose (normalized dose) Effect Source
dog LDLo intravenous 8mg/kg (8mg/kg) Cancer Chemotherapy Reports, Part 2. Vol. 2, Pg. 203, 1965.
rat LD50 subcutaneous 22mg/kg (22mg/kg) Kiso to Rinsho. Clinical Report. Vol. 5, Pg. 1894, 1971.
man TDLo oral 8mg/kg/2D-I (8mg/kg) behavioral: convulsions or effect on seizure threshold Lancet. Vol. 2, Pg. 1463, 1984.
rat LDLo oral 15mg/kg (15mg/kg) Khimiya i Meditsina. Vol. 13, Pg. 34, 1960.
rat LD50 intraperitoneal 18mg/kg (18mg/kg) Biochemical Pharmacology. Vol. 1, Pg. 39, 1958.
mouse LD50 oral 110mg/kg (110mg/kg) Kiso to Rinsho. Clinical Report. Vol. 5, Pg. 1894, 1971.
mouse LD50 intraperitoneal 86mg/kg (86mg/kg) Kiso to Rinsho. Clinical Report. Vol. 5, Pg. 1894, 1971.
mouse LD50 unreported 46mg/kg (46mg/kg) British Journal of Cancer. Vol. 6, Pg. 160, 1952.
rat LD50 intravenous 1800ug/kg (1.8mg/kg) Arzneimittel-Forschung. Drug Research. Vol. 20, Pg. 1467, 1970.
bird - wild LD50 oral 56200ug/kg (56.2mg/kg) Archives of Environmental Contamination and Toxicology. Vol. 12, Pg. 355, 1983.
mouse LD50 subcutaneous 63mg/kg (63mg/kg) Kiso to Rinsho. Clinical Report. Vol. 5, Pg. 1894, 1971.
women TDLo oral 80mg/kg/8Y (80mg/kg) JAMA, Journal of the American Medical Association. Vol. 238, Pg. 1951, 1977.
monkey LDLo intravenous 8mg/kg (8mg/kg) Cancer Chemotherapy Reports, Part 2. Vol. 2, Pg. 203, 1965.
rat LD50 unreported 10mg/kg (10mg/kg) Chemical Abstracts. Vol. 55, Pg. 10679a, 1961.


  • DrugBank DB01008
    CAS Number 134-63-4, 55-98-1
    PubChem Compound 2478