Saathoff N, Lode H, Neider K, Depperman K M, Borner K, Koeppe P
Department of Pulmonary and Infectious Medicine, City Hospital Zehlendorf, Berlin.
Antimicrob Agents Chemother. 1992 Apr;36(4):796-800. doi: 10.1128/AAC.36.4.796.
Cefpodoxime proxetil is a new oral esterified cephem antibiotic with a broad antibacterial spectrum. The dissolution of cefpodoxime proxetil is pH dependent. The objectives of this study were to characterize the pharmacokinetics of cefpodoxime proxetil in two different oral doses and to examine possible interactions with an antacid, aluminum magnesium hydroxide (Maalox 70), and an H2 receptor antagonist, famotidine. Two studies involving the same 10 healthy volunteers were performed. In the first study, cefpodoxime proxetil was administered in two doses, 0.1 and 0.2 g. In the second study, two interventions were performed in a randomized crossover design. For one intervention, the volunteers were pretreated with 40 mg of famotidine 1 h before 0.2 g of cefpodoxime proxetil was administered. In the second trial, participants were given 10 ml of Maalox 70 2 h and 10 ml of Maalox 70 15 min before they received 0.2 g of cefpodoxime proxetil. Serum and urine concentrations were determined by high-performance liquid chromatography. For the statistical evaluation, these data were tested by using the pharmacokinetics of 0.2 g of cefpodoxime proxetil from the first study. The maximum concentrations were 1.19 +/- 0.32 mg/liter after 0.1 g of cefpodoxime proxetil and 2.54 +/- 0.64 mg/liter after 0.2 g of cefpodoxime proxetil. The elimination half-lives were 149 min for 0.1 g and 172 min for 0.2 g of cefpodoxime proxetil. The total increase in the area under the concentration-time curve (AUC) was dose dependent. Combination with Maalox 70 caused a reduction in the AUC from 14.0 +/- 3.9 to 8.44 +/- 1.85 mg.h/liter. After famotidine, the AUC decreased to 8.36 +/- 2.0 mg . h/liter. Corresponding changes were registered for the maximum concentration of drug in serum, 24-h urine recovery, and the time to maximum concentration of drug serum. Cefpodoxime proxetil was well tolerated without any seriously adverse drug reactions.
头孢泊肟酯是一种新型的口服酯化头孢菌素类抗生素，抗菌谱广。头孢泊肟酯的溶出度取决于pH值。本研究的目的是表征两种不同口服剂量的头孢泊肟酯的药代动力学，并研究其与抗酸剂氢氧化铝镁（胃达喜70）和H2受体拮抗剂法莫替丁之间可能的相互作用。进行了两项涉及相同10名健康志愿者的研究。在第一项研究中，头孢泊肟酯以0.1 g和0.2 g两种剂量给药。在第二项研究中，采用随机交叉设计进行了两项干预。对于一项干预，志愿者在服用0.2 g头孢泊肟酯前1小时用40 mg法莫替丁预处理。在第二项试验中，参与者在接受0.2 g头孢泊肟酯前2小时和15分钟分别服用10 ml胃达喜70。血清和尿液浓度通过高效液相色谱法测定。为了进行统计评估，这些数据采用第一项研究中服用0.2 g头孢泊肟酯的药代动力学进行检验。服用0.1 g头孢泊肟酯后，最大浓度为1.19±0.32 mg/L，服用0.2 g头孢泊肟酯后为2.54±0.64 mg/L。头孢泊肟酯0.1 g的消除半衰期为149分钟，0.2 g的消除半衰期为172分钟。浓度-时间曲线下面积（AUC）的总增加量与剂量相关。与胃达喜70联合使用导致AUC从14.0±3.9降至8.44±1.85 mg·h/L。服用法莫替丁后，AUC降至8.36±2.0 mg·h/L。血清中药物的最大浓度、24小时尿液回收率以及药物血清达到最大浓度的时间也出现了相应变化。头孢泊肟酯耐受性良好，未出现任何严重的药物不良反应。
