Tam Y K, Kneer J, Dubach U C, Stoeckel K
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Antimicrob Agents Chemother. 1989 Jun;33(6):957-9. doi: 10.1128/AAC.33.6.957.
The pharmacokinetics of cefetamet pivoxil during administration of ascending oral doses were studied in 16 male normal healthy volunteers (age, 24.5 +/- 2.1 years; weight, 73.5 +/- 8.5 kg). The subjects were randomly assigned to four oral treatments of 500, 1,000, 1,500, and 2,000 mg of cefetamet pivoxil according to a four-by-four Latin square design. After an overnight fast, the drug was administered 10 min after a standard breakfast. It was found that both the rate and extent of prodrug absorption, measured as cefetamet adsorption, were reduced with increasing doses. The time to maximum concentration of cefetamet in serum was delayed from 4.00 +/- 0.81 to 4.88 +/- 0.96 h (P less than 0.05) when the dose of cefetamet pivoxil was increased from 500 to 2,000 mg. The dose-normalized values of area under the curve from 0 h to infinity for cefetamet and fraction of dose excreted as cefetamet were reduced by averages of 10.3 and 12.5%, respectively, over the dose range studied (P less than 0.05). The changes in rate and extent of prodrug absorption are thought to be the main factors contributing to the nonlinear relationship between maximum concentration in serum and dose. The change in absorption characteristics of cefetamet pivoxil with dose is, however, expected to have few clinical consequences because the magnitudes of these changes are comparable with their respective intragroup variations.
在16名男性健康志愿者（年龄24.5±2.1岁；体重73.5±8.5kg）中研究了口服递增剂量头孢他美酯匹伏酯期间的药代动力学。受试者根据4×4拉丁方设计随机分为4组，分别口服500、1000、1500和2000mg头孢他美酯匹伏酯。经过一夜禁食后，在标准早餐后10分钟给药。结果发现，以头孢他美吸附量衡量的前药吸收速率和程度均随剂量增加而降低。当头孢他美酯匹伏酯剂量从500mg增加到2000mg时，血清中头孢他美达峰时间从4.00±0.81小时延迟至4.88±0.96小时（P<0.05）。在所研究的剂量范围内，头孢他美0至无穷大曲线下面积的剂量归一化值和以头孢他美形式排泄的剂量分数分别平均降低了10.3%和12.5%（P<0.05）。前药吸收速率和程度的变化被认为是血清中最大浓度与剂量之间非线性关系的主要影响因素。然而，头孢他美酯匹伏酯吸收特性随剂量的变化预计对临床影响较小，因为这些变化的幅度与其各自组内变异相当。
