淫羊藿與Dapoxetine於大鼠體內之藥物動力學反應
薛又仁1,2,6,何靖凱3,林麗純4,邱文祥1,6,林奇宏5,蔡東湖2,7
1台北市立聯合醫院仁愛院區泌尿科
2國立陽明大學傳統醫學研究所
3國立陽明大學藥理學研究所
4國立中醫藥研究所
5國立陽明大學微生物免疫學研究所
6國立陽明大學醫學院醫學系泌尿學科
7高雄醫學大學藥學院藥學系
Herb-drug interaction of Epimedium extract on the pharmacokinetic of dapoxetine in rat
Thomas Y. Hsueh 1,2,3, †, Jing-Kai Ho 4, †, Lie-Chwen Lin 1,5, Allen W. Chiu 1,2, Chi-Hung Lin 6 and Tung-Hu Tsai 1,3,7,8*
1 Division of Urology, Department of Surgery, Taipei city Hospital Renai branch, Taipei, Taiwan
2 Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
3 Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan
4 National Research Institute of Chinese medicine, Ministry of Health and Welfare, Taipei, Taiwan
5 Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan
6 Department of Urology, School of Medicine, National Yang-Ming University, Taipei, Taiwan
7 School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
Purpose:
The aim of study is to develop a high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) method to investigate the pharmacokinetic interaction of Epimedium extract on the dapoxetine in rats.
Materials and Methods:
Experimental rats were divided into the following four parallel groups: (1) dapoxetine alone (10 mg/kg, i.v.); (2) oral administration of Epimedium extract (2 g/kg) for 3 consecutive days and on the fourth day dapoxetine was administered (10 mg/kg, i.v.); (3) dapoxetine alone (10 mg/kg, p.o.); (4) oral administration of Epimedium extract (2 g/kg) for 3 consecutive days and on the fourth day dapoxetine was administered (10 mg/kg, p.o.). The dapoxetine and internal standard (nylidrin) were determined by a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and separated by a C18 column (100 x 2.1 mm, 1.7 μm). The data was obtained in positive electrospray mode.
Results:
The calibration curves of dapoxetine were acquired over a concentration ranges from 1 to 500 ng/mL with the R2 = 0.999. The mean matrix effects and extraction recoveries of dapoxetine at three different concentrations (1, 10, 500 ng/mL) ranged from 107.3 to 110.9% and from 25.5 to 28.2% respectively. The interday and intraday relative standard deviation were both <6% while the bias were both <14%. The oral bioavailability of dapoxetine was about 75% in rat.
Conclusion:
The pharmacokinetic results demonstrated that pretreated with/without Epimedium extract for three consecutive days did not significant alter the pharmacokinetics of dapoxetine in rat.