头孢克肟3种剂型的人体生物等效性评价

Bioavailability of cefixime preparations using four-way crossover design experiments

目的评价试验制剂头孢克肟分散片、胶囊、片剂与参比制剂头孢克肟胶囊的单剂4交叉生物等效性试验。方法健康志愿者24名,随机分为4组,采用拉丁方试验设计,4周期随机交叉,自身对照,HPLC法测定头孢克肟经时血浓度,数据经DAS程序处理,得头孢克肟制剂药动学参数。结果试验制剂头孢克肟分散片、胶囊、片剂主要药动学参数T1/2分别为(5.552±0.555)、(5.495±0.630)和(5.480±0.673)h;tmax分别为(3.458±0.204)、(3.604±0.254)和(5.480±0.673)h;cmax分别为(3.727±1.417)、(3.723±1.529)和(3.675±1.386)mg.L-1;AUC0→24分别为(28.987±10.261)、(29.688±11.977)和(30.484±11.037)mg.h.L-1;AUC0→∞分别为(30.709±10.629)、(31.500±12.467)和(32.334±11.434)mg.h.L-1;相对生物利用度F分别为(97.478±8.967)%、(98.859±8.707)%和(102.186±7.959)%。参比制剂头孢克肟胶囊主要药动参数T1/2为(5.544±0.736)h,tmax为(3.625±0.338)h,cmax为(3.734±1.493)mg.L-1,AUC0→24为(29.882±11.117)mg.h.L-1,AUC0→∞为(31.675±11.450)mg.h.L-1。试验制剂与参比制剂tmax、T1/2、AUC0→∞、AUC0→24、cmax经方差分析、双向单侧t检验显示,主要药动学参数周期间、剂型间差异无显著性意义(P>0.05)。结论头孢克肟3种试验制剂与参比剂具有生物等效性。

AIM To evaluate bioequivalence of cefixime dispersants, capsules, tablets and cefixime reference capsules with four-way crossover design experiments. METHODS A single oral does of cefixime tested and reference tablets were given to 24 healthy volunteers in a randomized crossover study. The serum concentrations of cefixime dispersants, capsules, tablets and reference were determined by HPLC coupled with UV detector and their pharmacokinetic parameters were got after the data were calculated with “Drug And Statistics Ver 1”. RESULTS The pharmacokinetic parameters of cefixime dispersants, capsules, tablets and reference were as follows ： T1/2 was （5.552 ± 0. 555 ）, （ 5.495 ± 0. 630）, （5.480 ± 0.673） and （5.544 ± 0.736） h; tmax Was（3.458 ± 0.204）, （3.604 ± 0.254）, （3.583 ± 0.351） and （3.625 ± 0. 338） h; cmax was（3.727 ± 1.417） , （3.723 ± 1.529）, （3.675 ± 1.386） and （3. 734 ± 1. 493） mg· L^-1 ; AUC0→24 was（28.987 ± 10.261）,（29.688 ± 11.977）,（30.484 ± 11.037） and （29.882 ± 11.117） mg·h·L^-1 ;AUC0→∞ was（30.709 ± 10.629）,（31.500 ± 12.467）, （32.334 ± 11.434） and （31.675 ± 11.450） mg·h·L^-1 ,respectively. The relative bioavailability F was （97.478 ± 8.967） %, （98.859 ± 8.707）% and（ 102. 186 ± 7.959） %, respectively. Variance analysis and two one-sided test show that there were no significant differences between periods , individuals and preparations. CONCLUSION Cefixime tests and reference are bioequivalent.