Foulds G, Shepard R M, Johnson R B
Drug Metabolism Department, Pfizer Central Research, Groton, CT 06340.
J Antimicrob Chemother. 1990 Jan;25 Suppl A:73-82. doi: 10.1093/jac/25.suppl_a.73.
The pharmacokinetics of azithromycin, a new azalide antibiotic, were examined in man. Approximately 37% of a single oral dose of 500 mg was bioavailable and produced a peak serum concentration of 0.4 mg/l. Multiple dose regimens (two doses of 500 mg separated by 12 h and followed by 500 mg qds for five days, or two doses of 250 mg separated by 12 h and followed by 250 mg qds for nine days) produced only slight increases in peak serum concentrations. The serum protein binding of azithromycin declined from about 50% at 0.02 mg/l to 12% at 0.5 mg/l. Tissue concentrations of azithromycin were much higher than serum concentrations. After two 250 mg doses 12 h apart, peak azithromycin concentrations exceeded 3 mg/kg in prostate, tonsil and many other tissues. Concentrations in tissues declined with apparent half-lives of 2.3 days in prostate and 3.2 days in tonsil. The high tissue concentrations suggest that proposed standard dosage regimens of 500 mg qds on day 1 followed by 250 mg qds for four days, or three daily dosages of 500 mg, will produce tissue concentrations above 3 mg/kg in a variety of tissues. Since these tissue concentrations exceed the MICs of relevant pathogens, these dosage regimens should be effective against respiratory tract and soft-tissue infections. A single 1 g dose may be effective in the treatment of many sexually transmitted diseases.
对新型氮杂内酯类抗生素阿奇霉素在人体中的药代动力学进行了研究。单次口服500mg剂量时，约37%可被吸收，血清峰浓度为0.4mg/L。多剂量给药方案（两次500mg剂量，间隔12小时，随后500mg每日四次，共五天；或两次250mg剂量，间隔12小时，随后250mg每日四次，共九天）仅使血清峰浓度略有升高。阿奇霉素的血清蛋白结合率从0.02mg/L时的约50%降至0.5mg/L时的12%。阿奇霉素的组织浓度远高于血清浓度。间隔12小时给予两次250mg剂量后，前列腺、扁桃体和许多其他组织中的阿奇霉素峰浓度超过3mg/kg。组织中的浓度下降，前列腺中的表观半衰期为2.3天，扁桃体中的为3.2天。高组织浓度表明，建议的标准给药方案，即第1天500mg每日四次，随后250mg每日四次，共四天，或每日三次500mg，将在多种组织中产生高于3mg/kg的组织浓度。由于这些组织浓度超过了相关病原体的最低抑菌浓度（MIC），这些给药方案应能有效治疗呼吸道和软组织感染。单次1g剂量可能对许多性传播疾病有效。
