Klepser M E, Marangos M N, Patel K B, Nicolau D P, Quintiliani R, Nightingale C H
Department of Pharmacy Research, Hartford Hospital, Connecticut, USA.
Clin Pharmacokinet. 1995 May;28(5):361-84. doi: 10.2165/00003088-199528050-00003.
Several new cephalosporins have been developed in recent years. These agents include several oral and parenteral agents with extended activity against Gram-negative pathogens. The pharmacokinetic literature for these agents is quite extensive; therefore, we have summarised this information and presented it in tabular form for critical comparison. With a few exceptions, the newer cephalosporins share similar pharmacokinetic properties. Cefixime, cefetamet pivoxil and ceftibuten differ from the others in that they exhibit nonlinear pharmacokinetic properties. The nonlinear nature of these agents is reflected by decreasing maximal concentrations with escalating doses of cefixime and cefetamet pivoxil, decreasing area under the serum concentration-time curve with increasing doses for cefixime, and a reduced bioavailability with large doses of ceftibuten. Attention to such characteristics aid the clinician in selecting appropriate dosage regimens that will optimise drug absorption. The majority of agents are primarily renally eliminated; however, renal elimination accounts for only 20% of cefixime elimination. The pharmacokinetic parameters noted for the newer cephalosporins are not influenced by multiple-dose administration, suggesting lack of drug accumulation over time. The pharmacodynamics of antimicrobials should be considered when extrapolating pharmacokinetic information into the clinical arena. In the case of the beta-lactams, the time which drug concentrations remain above some critical threshold, such as the minimal inhibitory concentration, appears to have the greatest influence on bactericidal activity. Therefore, it is important to select dosage regimens that will optimise the time serum concentrations remain above this threshold. We present an evaluation of these agents with respect to their activity against a variety of pathogens in an effort to demonstrate a pharmacokinetically-based process of antimicrobial selection.
近年来已研发出几种新型头孢菌素。这些药物包括几种对革兰氏阴性病原体具有广泛活性的口服和肠胃外给药制剂。关于这些药物的药代动力学文献相当广泛；因此，我们总结了这些信息并以表格形式呈现，以便进行关键比较。除了少数例外，新型头孢菌素具有相似的药代动力学特性。头孢克肟、头孢他美酯和头孢布烯与其他药物不同，它们表现出非线性药代动力学特性。这些药物的非线性特性表现为，头孢克肟和头孢他美酯剂量增加时最大浓度降低，头孢克肟剂量增加时血清浓度 - 时间曲线下面积减小，以及大剂量头孢布烯时生物利用度降低。关注这些特性有助于临床医生选择能优化药物吸收的合适给药方案。大多数药物主要经肾脏消除；然而，肾脏消除仅占头孢克肟消除量的20%。新型头孢菌素的药代动力学参数不受多剂量给药影响，这表明不会随时间发生药物蓄积。将药代动力学信息外推至临床领域时应考虑抗菌药物的药效学。就β - 内酰胺类药物而言，药物浓度保持高于某个临界阈值（如最低抑菌浓度）的时间似乎对杀菌活性影响最大。因此，选择能优化血清浓度高于该阈值时间的给药方案很重要。我们对这些药物针对多种病原体的活性进行了评估，以展示基于药代动力学的抗菌药物选择过程。
