主催: 日本毒性学会
Piperine and its analogs have been reported as effective potentiators of anti-infective. SK-20: (5-(3,4 methylene dioxyphenyle)-4 ethyl-2E, 4E- pentadieonic acid piperidide) was earlier identified as the most potent efflux pump inhibitor and reported to have potentiating effects in the activity of etoposide by enhancing its oral bio availability. In the present study SK-20 was investigated for its toxicity profile and general pharmacology. SK-20 was found to be safe up to 2000 mg/kg and 100 mg/kg (b.wt.) when administered for acute exposure and sub-acute exposure respectively. However, histopathologicasl examination revealed some morphological alterations in the cellular architecture of liver and kidneys of animals in both sexes when treated at 200 mg/kg (b.wt.) of SK-20 during sub-acute exposure. These include mild vascular congestions along with sporadic hemorrhages and infiltration into renal and hepatic parenchyma by mononucleate cells. General pharmacological studies for analgesic, convulsions, rectal temperature and rhythm or the rate of the intestinal motility or the secretion of the bile did not showed significant changes up to the dose of 200 mg/kg. Although the rates of cardio- respiratory systems were normal, however, blood pressure showed a decreased pattern in dose dependent manner. Characteristically, SK-20, enhanced pentobarbital- induced hypnosis whereas a decrease was observed in the spontaneous motor activity dose dependently. A pharmacokinetic analysis of SK-20 revealed to have retention time at 10.2 minute and half life 2.47 hour. In conclusion this novel bioenhancer of piperine is a safe derivative at lower doses and not affecting the body physiology significantly.
