Finn A, Straughn A, Meyer M, Chubb J
Glaxo Inc., Research Triangle Park, N.C. 27709.
Biopharm Drug Dispos. 1987 Nov-Dec;8(6):519-26. doi: 10.1002/bdd.2510080604.
Cefuroxime axetil is an ester pro-drug which permits the oral administration of cefuroxime. This study was designed to evaluate the dose proportionality of four different doses administered after a meal and to determine the absolute bioavailability of cefuroxime axetil administered with and without food. The study was a six-way randomized crossover trial in 12 normal male volunteers. Subjects received an intravenous dose of cefuroxime (500 mg) and five oral doses of cefuroxime axetil (125, 250, 500-twice, 1000 mg). The intravenous dose and one of the 500 mg doses was administered after an overnight fast. The other four oral doses were administered after a standard meal. Blood samples were collected prior to each dose and serially for 12 h after the dose. Urine was collected for 24 h. Plasma and urine samples were analysed for cefuroxime by high pressure liquid chromatography. There was a linear relationship between the fed dose and both the area under the plasma concentration time curve (r2 = 0.958) and the peak plasma concentration (r2 = 0.943). Based on a comparison of the AUC for the oral and intravenous data, 36 per cent of the fasting and 52 per cent of the fed 500 mg doses were absorbed. The mean peak plasma concentration was 43 per cent greater after the fed dose than the fasting dose. A plot of the mean fraction of unabsorbed drug versus time reveals that absorption is an apparent zero order process from 0.5 to 3 h after dosing.
头孢呋辛酯是一种酯前体药物，可使头孢呋辛能够口服给药。本研究旨在评估餐后给予的四种不同剂量的剂量比例关系，并确定进食和未进食时服用头孢呋辛酯的绝对生物利用度。该研究是一项在12名正常男性志愿者中进行的六交叉随机试验。受试者接受了静脉注射剂量的头孢呋辛（500mg）和五个口服剂量的头孢呋辛酯（125、250、500mg——两次、1000mg）。静脉注射剂量和500mg剂量中的一个在禁食过夜后给药。其他四个口服剂量在标准餐后给药。在每次给药前采集血样，并在给药后连续12小时采集血样。收集尿液24小时。通过高压液相色谱法分析血浆和尿液样本中的头孢呋辛。进食剂量与血浆浓度-时间曲线下面积（r2 = 0.958）和血浆峰浓度（r2 = 0.943）之间均呈线性关系。根据口服和静脉注射数据的AUC比较，禁食时500mg剂量的36%以及进食时500mg剂量的52%被吸收。进食剂量后的平均血浆峰浓度比禁食剂量高43%。未吸收药物的平均分数与时间的关系图显示，给药后0.5至3小时内吸收是一个明显的零级过程。
