Toxicological evaluation of poloxamer vehicles for intramuscular use.

The muscle toxicity caused by injection of various poloxamer vehicles into the M. vastus lateralis of rabbits was investigated in single and multiple dose studies via gross morphological examination of the muscle tissue and by monitoring creatine phosphokinase (CPK) levels as a function of time following injection. Results were compared to those obtained for currently accepted intramuscular (IM) vehicles such as normal saline, cremophor EL, and peanut oil. The toxicity of the poloxamer vehicles was proportional to their lipophilicity; the more lipophilic the poloxamer, the more severe the lesion produced following injection and the greater the elevation in plasma CPK. Based on this preliminary study, it appears that poloxamer 407 and 238 may be suitable polymers for incorporation into vehicles for use as injectable gels for prolonged drug delivery.