氯化钾缓释片健康人体的生物等效性

Pharmacokinetics and relative bioavailability of modified-release tablets of potassium chloride in healthy volunteers

目的：建立火焰原子吸收分光光度法，研究氯化钾缓释片在健康人体的生物等效性。方法：试验采用两周期随机交叉试验设计，20名健康受试者分别口服试验制剂或参比制剂3．0g，每一周期给药后收集0～1，1～2，2～4，4～6，6～8，8～10，10～12，12～15，15～24h尿液，记录体积，取10mL于-20℃贮存备测。一周后重复上述试验。以给药后0～48h尿钾累积排泄量计算生物利用度，用方差分析和双单侧t检验和（1-2α）置信区间分析评价试验制剂和参比制剂的生物等效性。结果：氯化钾缓释片试验制剂与参比制剂主要药动学参数t1／2分别为（3．6±1．7）和（4．0±1．9）h，尿最大排泄量Amax分别为（7．7±1．8）mmol和（7．1±2．2）mmol，tmax分别为（5．4±2．3）h和（4．3±3．0）h，24h尿累积排泄总量分别为（28．5±5．2）mmol和（27．9±4．7）mmol。试验制剂氯化钾缓释片相对生物利用度F为（103．6±20．1）％。结论：2种氯化钾缓释片具有生物等效性。

OBJECTIVE To establish a flame atomic absorption spectrophotometry method for the determination of potassium in human urine. METHODS 20 healthy male volunteers were divided into two groups randomly according to a two period cross-over design test. Volunteers were orally given 3 g the test or reference preparations of potassium chloride tablets. The urine samples were collected at the following intervals： 0-1,1-2,2-4,4-6,6-8,8-10,10-12,12-15 and 15-24 h after administration. The volume of all the urine samples was recorded and 10 mL were stored at - 20 ℃ before use. The second period experiment was carried out same as above method 1 week＇s later. Analysis of variance, t-test and （1-2a） confidence interval were used to evaluate the bioequivalence of test and reference preparations. RESULTS The main pharmacokinetic parameters of test and reference preparations of potassium chloride sustained-release tablets were respectively as follows： t1/2 （3. 6 ± 1.7） and （4. 0 ± 1.9） h, the maximum excretion amount ,Amax （7.7 ± 1.8） and （7. 1 ± 2.2）retool, tmax （5.4 ± 2. 3） and （4. 3 ± 3.0）h, the accumulation excretion amount of 24 h after administration （28. 5 ± 5. 2） and （27. 9 ± 4. 7）mmol. The relative bioavailability of potassium chloride test preparation was （103.6 ± 20. 1） %. CONCLUSION The results demonstrate that the test and reference preparations are bioequivalent.