Preclinical Safety Assessment of #946;-Hydroxyphospho-Carnitine

β-hydroxyphospho-carnitine(β-HPC) has been shown therapeutic potential. However, safety information is lacking. Acute toxicity, chronic toxicity, embryotoxicity, teratogenicity and genotoxicity of β-HPC were evaluated. For the acute toxicity, β-HPC was orally administered to mice at a dose range of 5-9000 mg/kg. For the repeated dose toxicity study, male rats were orally administered with β-HPC at the doses of 100 mg/kg for a period of 24 weeks. The effects on body weight, food and water consumption, organ weight, hematology, clinical chemistry as well as histology were studied. For embryiotoxicity and teratogenicity, β-HPC was administered to fertile chicken eggs (range 60-480 μg/mL). The genotoxic potential was tested using a comet assay. Data of each parameter were analyzed by oneway ANOVA followed by Tukey-Kramer test to compare the difference between treated groups. In general toxicity studies, orally administered β-HPC showed no sign of toxicity in any of the analyzed parameters involved in rodent single- and repeated-dose studies. Chicken embryos exposed to β-HPC in ovo showed alterations in growth and development during the early stage and at the end of their development in a dose dependent manner. In some cases, embryonic development terminated at stages 40/45 on the Hamburger-Hamilton scale and there were no associated malformations. β-HPC was not genotoxic to THP-1 cells. The results of the toxicological research confirmed that the safety profile of β-HPC. This safety evaluation results support the implementation of an exploratory Phase I clinical trial and underscore the potential of β-HPC as a new drug.