Fraschini F, Scaglione F, Demartini G
Department of Pharmacology, University of Milan, Italy.
Clin Pharmacokinet. 1993 Sep;25(3):189-204. doi: 10.2165/00003088-199325030-00003.
Clarithromycin is a semisynthetic macrolide antibiotic, structurally related to erythromycin. It has a more favourable pharmacokinetic profile than erythromycin, thus allowing twice-daily administration and possibly increasing compliance among outpatients. Clarithromycin is well absorbed from the gastrointestinal tract and its systemic bioavailability (about 55%) is reduced because of first-pass metabolism. It undergoes rapid biodegradation to produce the microbiologically active 14-hydroxy-(R)-metabolite. The maximum serum concentrations of clarithromycin and its 14-hydroxy metabolite, following single oral doses, are dose proportional and appear within 3 hours. With multiple doses, steady-state concentrations are attained after 5 doses and the maximal serum concentrations of clarithromycin and of the 14-hydroxy derivative appear within 2 hours after the last dose. Clarithromycin is well distributed throughout the body and achieves higher concentrations in tissues than in the blood. Also, the 14-hydroxy metabolite exhibits high tissue concentrations, with values about one-third of the parent compound concentrations. The presence of food appears to have no clinically significant effect on clarithromycin pharmacokinetics. The main metabolic pathways are oxidative N-demethylation and hydroxylation, which are saturable and result in nonlinear pharmacokinetics. The primary metabolite (14-hydroxy derivative) is mainly excreted in the urine with the parent compound. A reduction in urinary clearance in the elderly and in patients with renal impairment is associated with an increase in area under the plasma concentration-time curve, peak plasma concentrations and elimination half-life. Mild hepatic impairment does not significantly modify clarithromycin pharmacokinetics. In conclusion, clarithromycin, because of its antibacterial activity and pharmacokinetic properties, appears to be a useful alternative to other macrolides in the treatment of community acquired infections.
克拉霉素是一种半合成大环内酯类抗生素，在结构上与红霉素相关。它具有比红霉素更有利的药代动力学特征，因此允许每日给药两次，并可能提高门诊患者的依从性。克拉霉素从胃肠道吸收良好，由于首过代谢，其全身生物利用度（约55%）降低。它经历快速生物降解以产生具有微生物活性的14-羟基-（R）-代谢物。单次口服给药后，克拉霉素及其14-羟基代谢物的最大血清浓度与剂量成正比，且在3小时内出现。多次给药时，在5次给药后达到稳态浓度，克拉霉素和14-羟基衍生物的最大血清浓度在最后一剂后2小时内出现。克拉霉素在全身分布良好，在组织中的浓度高于血液中的浓度。此外，14-羟基代谢物在组织中也表现出高浓度，其值约为母体化合物浓度的三分之一。食物的存在似乎对克拉霉素的药代动力学没有临床显著影响。主要代谢途径是氧化N-去甲基化和羟基化，这些途径是可饱和的，并导致非线性药代动力学。主要代谢物（14-羟基衍生物）主要与母体化合物一起经尿液排泄。老年人和肾功能损害患者的尿清除率降低与血浆浓度-时间曲线下面积、血浆峰浓度和消除半衰期增加有关。轻度肝功能损害不会显著改变克拉霉素的药代动力学。总之，由于其抗菌活性和药代动力学特性，克拉霉素似乎是治疗社区获得性感染时其他大环内酯类药物的有用替代品。
