Li Hua Huang1, Xiao Hong Xiong2, Yun Ming Zhong3, Mei Feng Cen4, Xuan Ge Cheng5, Gui Xiang Wang6, Lin Quan Zang7, Su Jun Wang8. 1. Department of pharmacology, School of pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: hlh1130@163.com. 2. Department of pharmacology, School of pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: 1373625459@qq.com. 3. Department of pharmacology, School of pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: ym12zhong@163.com. 4. Department of pharmacology, School of pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: 1147927559@qq.com. 5. Department of pharmacology, School of pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: 353280336@qq.com. 6. Department of pharmacology, School of pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: wgx306@aliyun.com. 7. Department of pharmacology, School of pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: 610253454@qq.com. 8. Department of pharmacology, School of pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: wsj7272@126.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Isochlorgenic acid C (IAC), one of the bioactive compounds of Lonicera japonica, exhibited diverse pharmacological effects. However, its pharmacokinetic properties and bioavailability remained unresolved. AIM OF THE STUDY: To determine the absolute bioavailability in rats and the dose proportionality on the pharmacokinetics of single oral dose of IAC. MATERIALS AND METHODS: A validated HPLC-MS method was developed for the determination of IAC in rat plasma. Plasma concentration versus time data were generated following oral and intravenous dosing. The pharmacokinetic analysis was performed using DAS 3.0 software analysis. Absolute bioavailability in rats was determined by comparing pharmacokinetic data after administration of single oral (5, 10 and 25mgkg(-1)) and intravenous (5mgkg(-1)) doses of IAC. The dose proportionality of AUC(0-∞) and Cmax were analyzed by linear regression. RESULTS: Experimental data showed that absolute oral bioavailability of IAC in rats across the doses ranged between 14.4% and 16.9%. The regression analysis of AUC(0-∞) and Cmax at the three doses (5, 10 and 25mgkg(-1)) indicated that the equations were y=35.23x+117.20 (r=0.998) and y=121.03x+255.74 (r=0.995), respectively. CONCLUSIONS: A new HPLC-MS method was developed to determine the bioavailability and the dose proportionality of IAC. Bioavailability of IAC in rats was poor and both Cmax and AUC(0-∞) of IAC had a positive correlation with dose. Evaluation of the pharmacokinetics of IAC will be useful in assessing concentration-effect relationships for the potential therapeutic applications of IAC.
ETHNOPHARMACOLOGICAL RELEVANCE: Isochlorgenic acid C (IAC), one of the bioactive compounds of Lonicera japonica, exhibited diverse pharmacological effects. However, its pharmacokinetic properties and bioavailability remained unresolved. AIM OF THE STUDY: To determine the absolute bioavailability in rats and the dose proportionality on the pharmacokinetics of single oral dose of IAC. MATERIALS AND METHODS: A validated HPLC-MS method was developed for the determination of IAC in rat plasma. Plasma concentration versus time data were generated following oral and intravenous dosing. The pharmacokinetic analysis was performed using DAS 3.0 software analysis. Absolute bioavailability in rats was determined by comparing pharmacokinetic data after administration of single oral (5, 10 and 25mgkg(-1)) and intravenous (5mgkg(-1)) doses of IAC. The dose proportionality of AUC(0-∞) and Cmax were analyzed by linear regression. RESULTS: Experimental data showed that absolute oral bioavailability of IAC in rats across the doses ranged between 14.4% and 16.9%. The regression analysis of AUC(0-∞) and Cmax at the three doses (5, 10 and 25mgkg(-1)) indicated that the equations were y=35.23x+117.20 (r=0.998) and y=121.03x+255.74 (r=0.995), respectively. CONCLUSIONS: A new HPLC-MS method was developed to determine the bioavailability and the dose proportionality of IAC. Bioavailability of IAC in rats was poor and both Cmax and AUC(0-∞) of IAC had a positive correlation with dose. Evaluation of the pharmacokinetics of IAC will be useful in assessing concentration-effect relationships for the potential therapeutic applications of IAC.