3种头孢地尼在健康人体内的生物等效性研究

The bioequivalence of 3 kinds of cefdinir preparations in healthy volunteers

目的建立测定人体血浆中头孢地尼浓度的UPLC-MS/MS方法,评价3种头孢地尼口服药物在健康人体内的生物等效性。方法随机、自身前后三交叉的试验设计。24名健康男性受试者单剂量口服3种头孢地尼100 mg,用UPLC-MS/MS法测定其血药浓度,计算主要药代动力学参数及相对生物利用度,评价3种药物的生物等效性。结果头孢地尼的线性范围为11.50~2300.00ng·m L^-1,批内、批间精密度（RSD）均小于10%。受试药物（片剂,分散片）与参比药物（胶囊）的主要药代动力学参数为,tmax分别为（3.00±0.80）,（3.20±0.90）和（3.50±0.70）h;Cmax分别为（548.96±184.58）,（607.09±236.38）和（570.18±172.37）ng·m L^-1;t1/2分别为（2.00±0.30）,（1.90±0.40）和（1.90±0.30）h,AUC0-t分别为（2755.35±956.10）,（3037.49±1014.42）和（2756.43±804.06）ng·m L^-1·h。头孢地尼片和头孢地尼分散片分别以胶囊为对照,相对生物利用度分别为（104.2±37.5）%和（111.8±30.3）%。结论建立的分析方法灵敏、快速、准确。3种头孢地尼在健康人体内的生物等效。

Objective To establish a high performance liquid chroma- tography -tandem mass spectrometry （UPLC -MS/MS） method to determination the plasma concentration of cefdinir and to study the pharmacokinctics and bioequivalence of three kinds of cefdinir formulations in healthy volunteers. Methods In a randomized, 3 way - crossover and selfcontrol study, 24 healthy male volunteers were orally administrated with three kinds of cefdinir formulations （ test sample and reference sample） 100 mg. The concentrations of cefdinir in plasma were determined by LC - MS/MS. The main pharmacokinetic parameters were calculated. Results The method was validated by investigating the accuracy and precision for intra and interday runs in a linear concentration from 11.50 -2300. 00 ng · mL^-1. The main pharmacokinetic parameters of test （cefdinir tables A drug, cefdinir dispersible tables B drug ） and reference （cefdinir capsules, C drug ） formulations in plasma were shown as follows： tmax were （3.00±0.80）, （3.20 ±0.90）and （3.50 ±0.70） h ; Cmax were （548. 96 ± 184. 58）, （607.09 ± 236. 38） and （570.18 ± 172.37） ng · mL^-1 ;t1/2 were （ 2. 00 ±0.30） ,（1.90 ±0.40）and （1.90 ±0. 30） h; AUC0-t were （2755.35 ±956.10）, （3037.49 ±1014.42） and （2756. 43 ± 804.06） ng · mL^-1 · h, respectively. The relative bioavailability F were （ 104.20 ±37.50）% and （ 111.50±29.70） %. Conclusion The method was proved to be accurate, rapid and sensitive. The three kinds of cefdinir formulations are bioequivalent in healthy volunteers.