高脂高热量饮食对头孢呋辛酯片药动学的影响

Effects of High-fat and High-calorie Diets on Pharmacokinetics of Cefuroxime Axetil Tablets

目的研究高脂肪高热量饮食对头孢呋辛酯在健康受试者体内的药动学的影响。方法采用随机、开放、单剂量给药、双交叉试验设计。12例健康男性受试者随机分为两组,每组6人,分别空腹和餐后服用头孢呋辛酯片250 mg,给药前后按不同采血时间点采集血样,采用液相色谱-质谱联用(HPLC-MS/MS)法测定血浆中头孢呋辛浓度,用DAS3.2.8软件计算药动学参数,并用DAS3.2.8软件和SPSS19.0软件对其主要参数进行统计分析。结果空腹与餐后的主要药动学参数如下:AUC_(0-t)分别为(11 402.8±3 556.7)和(18 565.7±2 917.9)ng·h·mL^(-1),AUC_(0→∞)分别为(11 492.5±3 581.8)和(18 754.7±2 885.6)ng·h·mL^(-1),ρ_(max)分别为(3 406.7±1 188.9)和(5 439.2±1 118.2)ng·mL^(-1),t_(max)分别为(2.01±0.64)和(2.08±0.79)h,t_(1/2)分别为(1.66±0.38)和(1.60±0.60)h。用SPSS19.0软件对空腹和餐后给药的主要药动学参数进行统计分析,AUC_(0-t)、AUC_(0→∞)和ρ_(max)具有显著性差异(P<0.01),t_(max)与t_(1/2)无统计学意义(P>0.05)。ρ_(max)、AUC分别升高了59.7%和63.2%,t_(max)几乎不变。用DAS3.2.8软件进行等效性分析,AUC_(0-t)比值(餐后/空腹)的90%置信区间为137.6%~217.5%,AUC_(0→∞)比值(餐后/空腹)的90%置信区间为138.4%~217.3%,ρ_(max)比值(餐后/空腹)的90%置信区间为135.4%~207.6%,均不在80%~125%等效区间内。结论高脂高热量饮食可显著提高头孢呋辛酯片在人体内的吸收程度,但不影响其吸收速度。

OBJECTIVE To investigate the effect of high-fat and high-calorie diets on pharmacokinetics of cefuroxime axetil in healthy Chinese subjects. METHODS A randomized, open-label, single dose and two-way crossover clinical study was conducted. Twelve healthy subjects were randomly divided into two groups, each of which includes six males, then they were given 250 mg of cefu- roxime axetil respectively before and after meal. Blood samples were collected at different time points before and after drug administra- tion. The concentration of cefuroxime in plasma was determined by HPLC-MS/MS. The pharmacokinetic parameters were calculated by DAS3.2. 8 and were analyzed by DAS3.2. 8 and SPSS19.0. RESULTS The main pharmacokinetic parameters of fasting and post- prandial were as follows ： AUC0_t was （ 11 402. 8 ± 3 556. 7 ） and （ 18 565.7 ± 2 917. 9 ） ng·h·mL-1, AUC0-xwas （ 11 492. 5 ± 3 581.8） and （18 754.7±2885.6） ng·h·mL-1,pmaxwas （3 406.7±1 188.9） and （5 439.2＋1 118.2）ng·h·mL-1, t was （2. 01±0. 64） and （2. 08 ±0. 79） h, tl/2 was （1.66 ±0. 38） and （1.60 ±0. 60） h, respectively. The main pharmaeokinetic param- eters between fasting and high-fat meal groups were analyzed by SPSS19.0 software. There was significant difference in AUCo-x, AUC0-x and pmax（P 〈0. 01 ） , and no significant difference in tmax and tl/2 （P 〉0. 05）. The Pm and AUC were increased by 59. 7% and 63.2% respeetively, t is almost unehanged. The equivalence analysis was performed with DAS. 3.2. 8 software, the 90% confi- denee intervals for the ratios of AUC0-x AUC0-x and p for the postprandial/fasting were 137.6% -217.5% , 138.4% - 217.3% , 135.4% - 207.6% , respectively. None of them fall within the aceeptable interval of 80% - 125%. CONCLUSION High-fat and high-calorie diets can significantly improve the extent of absorption of cefuroxime axetil in vivo, but does not affect the absorption rate of cefuroxime axetil.