Kim Yo Han, Choi Hee Youn, Lee Shi Hyang, Jeon Hae Sun, Lim Hyeong-Seok, Bahng Mi Young, Bae Kyun-Seop
Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea.
Clinical Development Department, Dong-A ST Co, Ltd, Seoul, Republic of Korea.
Drug Des Devel Ther. 2015 Feb 23;9:1209-16. doi: 10.2147/DDDT.S78713. eCollection 2015.
"Udenafil" is a phosphodiesterase-5 inhibitor indicated for erectile dysfunction. "Dapoxetine" is a serotonin transport inhibitor indicated for premature ejaculation. The aim of the study reported here was to investigate the pharmacokinetic drug interaction between udenafil and dapoxetine in healthy male subjects.
An open-label, three-treatment, six-sequence, three-period crossover study was performed in healthy male subjects. In varying sequences, each subjects received single oral doses of udenafil 200 mg, dapoxetine 60 mg, and both treatments. The periods were separated by a washout period of 7 days. Serial blood samples were collected up to 48 hours after dosing. The plasma concentrations of udenafil and dapoxetine were determined using a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were obtained by non-compartmental analysis. Tolerability was assessed throughout the study.
Twenty-three healthy subjects completed the study. The geometric mean ratios of the area under the plasma concentration-time curve from time 0 to last measurable time point and measured peak plasma concentration for udenafil were 0.923 (90% confidence interval [CI]: 0.863-0.987) and 0.864 (90% CI: 0.789-0.947), respectively. The geometric mean ratios of the area under the plasma concentration-time curve from time 0 to last measurable time point and measured peak plasma concentration for dapoxetine were 1.125 (90% CI: 1.044-1.213) and 0.837 (90% CI: 0.758-0.925), respectively. There were no serious adverse events reported, and none of the subjects dropped out due to adverse events.
Udenafil was found to have no clinically significant pharmacokinetic interactions with dapoxetine. The concurrent administration of udenafil and dapoxetine was generally well tolerated.
“伐地那非”是一种用于治疗勃起功能障碍的磷酸二酯酶-5抑制剂。“达泊西汀”是一种用于治疗早泄的5-羟色胺转运抑制剂。本文所报道研究的目的是调查健康男性受试者中伐地那非与达泊西汀之间的药代动力学药物相互作用。
在健康男性受试者中进行了一项开放标签、三治疗、六序列、三周期交叉研究。按照不同序列，每位受试者接受单剂量口服200mg伐地那非、60mg达泊西汀以及两种药物联合治疗。各周期之间间隔7天的洗脱期。给药后长达48小时内采集系列血样。采用经过验证的液相色谱-串联质谱法测定伐地那非和达泊西汀的血浆浓度。通过非房室分析获得药代动力学参数。在整个研究过程中评估耐受性。
23名健康受试者完成了研究。伐地那非从0时到最后可测量时间点的血浆浓度-时间曲线下面积的几何平均比值以及实测的血浆峰浓度分别为0.923（90%置信区间[CI]：0.863 - 0.987）和0.864（90%CI：0.789 - 0.947）。达泊西汀从0时到最后可测量时间点的血浆浓度-时间曲线下面积的几何平均比值以及实测的血浆峰浓度分别为1.125（90%CI：1.044 - 1.213）和0.837（90%CI：0.758 - 0.925）。未报告严重不良事件，且无受试者因不良事件退出研究。
发现伐地那非与达泊西汀不存在具有临床意义的药代动力学相互作用。伐地那非与达泊西汀联合给药总体耐受性良好。
