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Pharmacokinetics Analysis of Copen, a Novel Antitumor Semi Synthetic Derivative of Osthole, in Rats after Intragastric and Intravenous Administration

Zheng Y, Zhou H, Hu X, Wu G, Yanan L and Shentu J

Copen is one of the major semi synthetic derivatives of osthole with obvious antitumor activity. The absolute bioavailability and gender-related pharmacokinetic properties of copen in rats were determined in this study. Sprague-Dawley rats were intragastrically and intravenously administrated of different doses of copen, respectively. The concentrations of copen in rat plasma were determined by a LC-MS/MS method. Pharmacokinetic parameters were estimated using a drug and statistics (DAS) software. Statistical analysis was performed using independent two-sample t-test with p-values less than 0.05 as the level of significance. The results indicated that maximum plasma concentrations (Cmax) for copen were achieved at 9.17-14.17 min post-intragastric dosing; the elimination half-life (t1/2z) of copen after intragastric dosing was 196.55-302.16 min. After intragastric administration of copen, the spearman's rank correlation coefficient (rs) of Cmax-Dose was 0.49810 (p=0.0023), and the rs of AUC0-t-Dose was 0.74634 (p<0.0001). Significant differences (p<0.05) of AUC0-t, AUC0-∞, CLz/F and Cmax were present in female and male groups after intragastric doses. Absolute bioavailability of copen was assessed to be ranged from 2.21- 10.67% for different doses in rats. The pharmacokinetic properties of copen in rat were characterized as rapid oral absorption, slow clearance, and significant gender differences.