Chemistry:Butafosfan
Butafosfan is [1-(butylamino)-1-methylethyl-phosphonic acid. The substance is an organophosphorus compound used as a phosphorus source in cattle, horses, pigs, sheep and goats, but the establishment of MRLs[disambiguation needed] was requested for non-lactating cattle only. The major indications are disorders of the metabolism, especially in young animals. It is also applied to support the treatment of infertility, tetany and paresis as an adjunct to calcium and magnesium therapy. To cattle butafosfan is administered as a single dose of 1000 to 2500 mg/animal by intravenous, intramuscular or subcutaneous route and the treatment may be repeated daily if required. Two veterinary medicinal products that are registered within the EU contain butafosfan in combination with either calcium and magnesium salts or vitamin B12. No specific data on the pharmacological activities of butafosfan were provided. The precise mode of action of butafosfan is unknown and it is questionable whether the effect of butafosfan is simply a matter of the substitution of phosphorus.[1]
Pharmacokinetics
The intravenous administration of butafosfan to cattle at a dose level of 5.6 mg/kg bw as a single dose resulted in a pharmacokinetic profile in serum corresponding to a three-compartment model. Three half-lives were calculated to 1.7 minutes, 13.2 minutes and 1.38 hours; the latter describing the terminal elimination process. Urine is the major route of excretion of butafosfan and a mean of 74% and 0.2% of parent compound was recovered in urine and feces respectively, within the first 12 hours. This study was not radiolabelled, but was conducted in accordance with GLP standards and the analyses were performed with liquid chromatography-tandem mass spectrometry (LC-MS/MS).
No pharmacokinetic studies were performed after intramuscular or subcutaneous administration.
The acute toxicity of butafosfan is very low. The oral LD50 in mice was approximately 16 000 mg/kg bw. After parenteral administrations, the following LD50 values were obtained in mice: approximately 21 000 mg/kg bw (subcutaneously), approximately 10 000 mg/kg bw (intravenously) and greater than 2500 mg/kg bw (intraperitoneally). Mice dosed orally or subcutaneously died within 3 and 2 days, respectively, while survivors had recovered by that time. The LD50 value in chicken (intramuscularly) was 9974 mg/kg bw. Observed toxic signs were excitation, cyanosis, sternal recumbency and diarrhea.[1]
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