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: AUC0-t分别为(11 402.8±3 556.7)和(18 565.7±2 917.9)ng·h·mL-1,AUC0-∞分别为(11 492.5±3 581.8)和(18 754.7±2 885.6)ng·h·mL-1,ρmax分别为(3 406.7±1 188.9)和(5 439.2±1 118.2)ng·mL-1,tmax分别为(2.01±0.64)和(2.08±0.79)h,t1/2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,AUC0-t、AUC0-∞和ρmax具有显著性差异(P<0.01),tmax与t1/2无统计学意义(P>0.05)。ρmax、AUC分别升高了59.7%和63.2%,tmax几乎不变。用DAS3.2.8软件进行等效性分析,AUC0-t比值(餐后/空腹)的90%置信区间为137.6%~217.5%,AUC0-∞比值(餐后/空腹)的90%置信区间为138.4%~217.3%,ρmax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。
Abstract
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 cefuroxime axetil respectively before and after meal. Blood samples were collected at different time points before and after drug administration. 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 postprandial were as follows: AUC0-t was (11 402.8±3 556.7) and (18 565.7±2 917.9) ng·h·mL-1, AUC0-∞ was (11 492.5±3 581.8) and (18 754.7±2 885.6) ng·h·mL-1, ρmax was (3 406.7±1 188.9) and (5 439.2±1 118.2) ng·mL-1, tmax was (2.01±0.64) and (2.08±0.79) h, t1/2 was (1.66±0.38) and (1.60±0.60) h, respectively. The main pharmacokinetic parameters between fasting and high-fat meal groups were analyzed by SPSS19.0 software. There was significant difference in AUC0-t, AUC0-∞ and ρmax(P<0.01), and no significant difference in tmax and t1/2 (P>0.05). The ρmax and AUC were increased by 59.7% and 63.2% respectively, tmax is almost unchanged. The equivalence analysis was performed with DAS.3.2.8 software, the 90% confidence intervals for the ratios of AUC0-t, AUC0-∞ and ρmax for the postprandial/fasting were 137.6%-217.5%, 138.4%-217.3%, 135.4%-207.6%, respectively. None of them fall within the acceptable 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.
关键词
头孢呋辛酯 /
高脂肪高热量饮食 /
液相色谱-质谱联用法 /
药动学
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Key words
cefuroxime axetil /
high-fat and high-calorie diets /
HPLC-MS/MS /
pharmacokinetics
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中图分类号：
R969.1
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参考文献
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