口服托伐普坦片对男性健康志愿者的药效学作用及其对血电解质的影响  

Diuretic and electrolyte effects of oral tolvaptan tablets in healthy male Chinese volunteers

作　　者：贾友宏[1] 许莉[1] 田蕾[1] 蒋娟娟[1] 李娜[1] 华丛笑[1] 谢爽[1] 刘红[1] 黄一玲[1] 张阴凤[1] 陈欣[1] 李一石[1] 

机构地区：[1]中国医学科学院阜外心血管病医院卫生部心血管药物临床研究重点实验室,北京100037

出　　处：《中国新药杂志》2008年第2期160-164,共5页Chinese Journal of New Drugs

基　　金：国家科技支撑计划课题(2006BAI14B07)

摘　　要：目的：评价血管升压素受体拮抗剂托伐普坦片对中国健康男性的药效作用和其对血电解质的影响。方法：入选健康男性39名，分四组分别单次口服托伐普坦片15mg（n=9），30mg（n=10），60mg（n=10）和120mg（n=10），观察48h内的尿量、血电解质浓度、饮水量变化，以及服药24h后的体重变化和不良事件。结果：①受试者体重无明显改变，统计学比较无差异。②服药6h内，6～12h，12～24h和24～48h的4组尿量分别为15mg组：（1921±496），（2977±389），（3680±724），（3948±398）；30mg组：（1361±500），（2631±661），（3492±1094），（4518±802）；60mg组：（1268±868），（2167±1074），（2267±1088），（3981±1667）；120mg组：（1302±624），（2643±1100），（2460±660），（4394±1132）mL。③血清氯、钠浓度24h内有升高，48h恢复服药前水平，氯浓度升高超过正常高限（大于110mmol·L^-1），但未需处理。血钠浓度略高，血钾浓度略低，均在正常范围内变化，无临床意义改变。（梦血压，心率无明显影响；共有13例次（13／39，33．3％）有口干和口渴的症状，程度轻中度可以耐受。未见严重不良事件。结论：单剂口服托伐普坦片15，30，60或120mg均有较强的排水利尿作用，且可持续24h，有剂量依赖性。Objective： To evaluate the diuretic and electrolyte effects of 4 different doses of tolvaptan in healthy male Chinese volunteers. Methods： Thirty-nine healthy men were randomly divided to four groups, and orally administered with tolvaptan at single dose of 15 mg （n = 9）, 30 mg （n = 10）, 60 mg （ n = 10）, or 120 mg （n = 10）. The changes in urine volumes, serum concentrations of electrolytes and water drink volumes were observed; the body weight （BW） and adverse events were also observed during 48 h. Results： The average BW did not change significantly （P 〉0.05）. The urine volumes （mL） during 0 -6 h, 6 -12 h, 12 -24 h and 24 -48 h were （1921 ±496）, （2977±389）, （3 680 ±724）, （3 948±398） after taking 15 mg; （1 361±500）, （2 631±661）, （3 492± 1 094）, （4 518±802） after taking 30 mg; （1 268±868）, （2 167 ±1 074）, （2 267 ± 1 088）, （3981±1 667） after taking 60 mg; （1 302 ±624）, （2643 ±1 100）, （2460±660）, （4394 ±1 132） after taking 120 mg, respectively. The serum chloride and sodium concentrations were significantly increased at 24 h but recovered at 48 h after administration; especially the serum chloride was over the normal range （ 〉 110 mmol·L ^-1） but did not need to treat. The serum concentration of sodium was increased and that of potassium was decreased slightly, but they were within the normal ranges without clinical significance. Blood pressure and heart rate did riot change significantly. Mild and moderate dry mouth and/or thirsty occurred in 13/39 volunteers （33.3%）, but the symptoms were well tolerated. No severe adverse events were observed. Conclusion： Single doses of tolvaptan （15 mg, 30 mg, 60 mg or 120 mg） exert a strong diuretic effect that lasts for 24 h and is dose-dependent in healthy male Chinese volunteers; it also increases serum chloride concentration significantly but is well tolerated.

关 键 词：托伐普坦 利尿作用 血电解质 不良事件 

分 类 号：R972[医药卫生—药品]