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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 effects of high fat and high calorie diet on the pharmacokinetics of cefuroxime axetil in healthy volunteers. Methods Randomized, open, single dose administration, double crossover design. Twelve healthy male subjects were randomly divided into two groups with 6 in each. The patients were given 250 mg of cefuroxime axetil fasting and after meals respectively. Blood samples were taken before and after different time of blood sampling. Liquid chromatography - mass spectrometry The concentration of cefuroxime in plasma was determined by HPLC-MS / MS. The pharmacokinetic parameters were calculated by DAS3.2.8 software and the main parameters were analyzed by DAS3.2.8 software and SPSS19.0 software. Results The main pharmacokinetic parameters of fasting and postprandial were as follows: AUC 0-t were (11 402.8 ± 3 556.7) and (18 565.7 ± 2917.9) ng · h · mL -1, AUC 0 → ∞) were (11 492.5 ± 3 581.8) and (18 754.7 ± 2885.6) ng · h · mL -1, respectively, and the max values were (3 406.7 ± 1 188.9) and (5 439.2 ± 1 118.6 ng · mL -1 and t max respectively were (2.01 ± 0.64) and (2.08 ± 0.79) h and (t 1/2) were 1.66 ± 0.38 and 1.60 ± 0.60 respectively . The main pharmacokinetic parameters of fasting and postprandial administration were statistically analyzed by SPSS19.0 software. There was significant difference (P <0.01) between AUC_ (0-t), AUC_ (0 → ∞) and ρ_ (max) t_ (max) and t_ (1/2) were not statistically significant (P> 0.05). ρ_ (max), AUC increased 59.7% and 63.2%, respectively, while t_ (max) hardly changed. The equivalent AUC_ (0-t) (postprandial / fasting) 90% confidence interval was 137.6% -217.5% with the AUC_ (0 → ∞) ratio (postprandial / fasting) 90% confidence interval was 138.4% ~ 217.3%, and the 90% confidence interval of ρ max ratio (postprandial / fasting) was 135.4% ~ 207.6%, which were all within the equivalent range of 80% ~ 125%. Conclusion High-fat and high-calorie diet can significantly improve the absorption of cefuroxime axetil tablets in the human body, but does not affect the absorption rate.