Pharmacokinetic Study Of Verticinone And Cholic Acid-verticinone Ester In Rats

Verticinone has a good expectorant, antiasthmatic, antitussive pharmacological activity, however, its toxic side effects prevent it to develop into a new drug. Cholic acid-Verticinone ester (CA-Ver), the compound from verticinone via structural transformation, still has good expectorant, antiasthmatic, antitussive pharmacological activity, but the toxicity is significantly lower than verticinone, hence, CA-Ver has a better development prospect. In order to learn the kinetic behaviors of CA-Ver in vivo, and then to elaborate its pharmacological effects to the body, meanwhile, find the reason why the toxicity of CA-Ver is lower than verticinone, we have developed a sensitive and reproducible method for determination and pharmacokinetic study of verticinone and CA-Ver in rat plasma using high performance liquid chromatography- mass spectrometric (HPLC-MS) method.The method was with good linearity in the range of 0.01-4ng·ml^-1and 2^-128ng·ml^-1,and the r values were 0.9990 and 0.9995, respectively. The average extract recoveries of three different concentrations of verticinone from rat plasma were all no less than 85%, the specificity, accuracy, precision and quantitative range were all within the required limits. The rat plasma with verticinone was stable under the frozen condition and the residue had good stability, whatever, in the frozen or at room temperature, so the stability of samples could meet the experimental need. This HPLC-MS method was successfully applied to pharmacokinetic study of verticinone and CA-Ver for oral administration in SD rats.The pharmacokinetic parameters were acquired via using DAS 2.0 software to calculate in accordance with non-compartmental model, according to the plasma concentration - time cure. The results showed that the absorptions of theses two compounds in rats had obvious difference between the male and female. And AUC and administration dose positively correlated, The r values were 0.991(verticinone, male rats), r=0.945 (verticinone, female rats), r=0.941(CA-Ver, male rats), r=0.983 (CA-Ver, female rats), respectively, which showed that the pharmacological effects of these two compounds were enhanced by direct proportion with the administration doses in ratsThe results showed that when the rats, whether the male or the female, were oral administrated verticinone (4.3mg·kg^-1) and CA-Ver (8.2 mg·kg^-1) with equal molar mass, the peak time of verticinone was faster than CA-Ver, but the elimination half-time was similar. And AUC0～25 of verticinone was also greater than that of CA-Ver, which proved that the degree of verticinone absorption in vivo is bigger than that of CA-Ver. From the results, we can explain the reason for that the toxic of Verticinone is greater than CA-Ver.