Pharmacodynamic and pharmacokinetic evaluation Of verbenone in normal and ovalbumin induced Asthmatic rats

Abstract

Verbenone is a naturally occurring anti-aggregation pheromone generated by bark newlinebeetles from a host tree resin precursor, and#61537;-pinene. Asthma is a common chronic disorder of newlinethe airways that is complex and characterized by variable and recurring symptoms, airflow newlineobstruction, bronchial hyper-responsiveness, and an underlying inflammation. In the current newlinestudy, the acute toxicity at the rate of 2000 mg/kg body weight single oral dosing, sub acute newlinetoxicity at the rate of 200 mg/kg oral dosing for 30days, pharmacokinetics of verbenone in newlinenormal healthy as well as ovalbumin-induced asthmatic animals and pharmacodynamic newlineactivity of verbenone in healthy and asthmatic animals were done. It was found that the newlineverbenone did not produce any toxicity at the dose rate of 2000 mg/kg single oral dose newlinemaking it a practically non toxic compound. Besides, repeated dose administration for 30 newlinedays at the dose rate of 200 mg/kg orally also did not produce any appreciable toxicity. It was newlinealso found that the drug did not produce any central nervous system effects as evidenced by newlinelack of variation in spontaneous locomotor activity. newlineIn single dose non-compartmental pharmacokinetics in rats, it was found that the newlinemean terminal elimination rate constant was 0.133±0.030/ h, mean elimination t1/2 of newline4.368±0.888 hours, observed mean AUC0-inf was 1.361 ± 0.0520 and#956;g/ml*h, observed AUMC0- newlineinf was 6.441± 0.6356 and#956;g/ml*h2, mean residence time was 6.304± 0.385 hours, Cmax and Tmax newlinewere 0.497±0.049 and#956;g/ml and h hour, respectively. Apparent volume of distribution during newlineterminal phase was 1134.798± 161.65 (mg)/(and#956;g/ml) and apparent total body clearance of the newlinedrug from plasma was 147.1769±5.645 (mg)/(and#956;g/ml)/h. Comparing the pharmacokinetics in newlinenormal and asthmatic animals it was found that though the Tmax did not change in disease newlinecondition all other parameters were significantly altered. In asthmatic animals maximum newlineplasma concentration changed from 0.497 ± 0.049 to 0.322 ± 0.015 and#956;g/ml. The AUC0-inf had newlinereduced from 1.361 ± 0.052 to 0.828 ± 0.012 and#956;g/ml*h