OBJECTIVE: To investigate the effect of dining on the pharmacokinetics of losartan in healthy volunteer after single oral dose of Losartan potassium tablets. METHODS: 10 healthy volunteers were randomly divided into 2 groups with each group of 5 persons. One group received 50 mg Losartan potassium tablet at once after fasting 10 hours. Another group received 50 mg Losartan potassium tablet at once after dinner. Cross randomized test was designed after 1 week cleaning. The plasma concentrations of losartan and its metabolite E-3174 were determined by HPLC-MS/MS. DAS 2.1.1 sofivare was adopted to calculate pharmacokinetic parameters and the effect of dinning and fasting on pharmacokinetics of losartan were compared. RESULTS: Under the condition of fasting vs. dining, the main pharmacokinetic parameters of losartan were as follows: tmax (1.33 ± 0.60) h vs. (2.20 ±1.09) h; cmax(268.51 ± 192.39)μg.L-1vs. ( 138.11 ± 32.84)μg·L-1; AUC0～12(442.83 ± 171.05) μg·h·L-1 vs. (401.54 ± 98.43) μg·h·L-1; t1/2x( 1.59 ± 0.22) h and ( 1.74± 0.59)h; MRT0～12(2.74 ± 0.69) h vs.(3.~7 ± 0.91 ) h. The main pharmacokinetic parameters of metabolite E-3174 of losartan were as follows: cmax(890.6 ± 239.13) . tg·L-1 vs. (904.9 ± 415.88)μg. L-1; tmax(4.60 ± 1.58) h vs.(5.00 ± 1.41) h; AUC00～36(6 407.54 ± 1 243.00)μg·h·L-1 vs. (~ 417.02 ± 2 472.92) μg·h·L-1; t1/2z(5.25 ± 3.40) h vs. (4.04 ± 1.40)h; MRT0～36(8.34 ± 1.52) h vs. (8.95 ± 1.24)h. There were no significant differences between two groups for all above pharmacokinetic parameters in t-test(P＞0.05). CONCLUSION: The pharmacokinetic parameters of losartan and its metabolite E-3174 which plays the main hypotensive effect have no significant difference under the condition of fasting and dinning. Dining has no statistically significant effect on the metabolism of losartan.%目的:研究进食对健康受试者单剂量口服氯沙坦钾片药动学的影响.方法:10名健康受试者随机分为2组,每组5人.试验开始前一晚禁食10h,晨起后,一组空腹口服氯沙坦钾片50mg,另一组在进食后口服氯沙坦钾片50mg.经1周清洗期后,两组交叉试验.采用高效液相色谱串联质谱电喷雾(HPLC-MS/MS)法测定人血浆中氯沙坦及其代谢产物E-3174的浓度,采用DAS2.1.1软件计算药动学参数并比较进食或空腹对药动学的影响.结果:空腹和进食后服用氯沙坦钾片,血浆原型药物tmax分别为(1.33±0.60)、(2.20±1.09)h,cmax 分别为(268.51±192.39)、(138.11±32.84)μg·L-1,AUC0～12分别为(442.83±171.05)、(401.54±98.43)μg·h·L-1,t1/2z分别为(1.59±0.22)、(1.74±0.59)h,MRT0～12分别为(2.74±0.69)、(3.57±0.91)h;代谢产物E-3174的cmax分别为(890.6±239.13)、(904.9±415.88)μg·L-1,tmax分别为(4.60±1.58)、(5.00±1.41)h,AUC0～36分别为(6 407.54±1 243.00)、(6 417.02±2 472.92)μg·h·L-1,t1/2z分别为(5.25±3.46)、(4.64±1.46)h,MRT0～36分别为(8.34±1.52)、(8.95±1.24)h.上述药动学参数差异经t检验无统计学意义(P＞0.05).结论:空腹和进食后服用氯沙坦钾片,原型药物和起主要降压作用的代谢产物E-3174的各药动学参数无显著性差异,可认为进食对本药在健康人体内的代谢无影响.
展开▼
