THE PHARMACOKINETICS OF AZITHROMYCIN IN HUMAN SERUM AND TISSUES
THE PHARMACOKINETICS OF AZITHROMYCIN IN HUMAN SERUM AND TISSUES
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DOI：
10.1093/jac/25.suppl_a.73
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发表时间：
1990-01-01
影响因子：
5.2
通讯作者：
JOHNSON, RB
中科院分区：
文献类型：
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作者：
FOULDS, G;SHEPARD, RM;JOHNSON, RB
研究了新氮杂内酯类抗生素阿奇霉素的人体药代动力学，单次口服500 mg阿奇霉素约有37%的生物利用度，血药峰浓度为0.4 mg/l。多次给药方案（500 mg两次给药，间隔12小时，随后500 mg qd给药5天，或250 mg两次给药，间隔12小时，随后250 mg qd给药9天）仅导致血清峰浓度轻微升高。阿奇霉素的血清蛋白结合率从0.02 mg/l时的约50%降至0.5 mg/l时的12%。阿奇霉素的组织浓度远高于血清浓度。在间隔12小时的两次250 mg剂量后，前列腺、扁桃体和许多其他组织中的阿奇霉素峰值浓度超过3 mg/kg。组织中的浓度下降，前列腺中的表观半衰期为2.3天，扁桃体中的表观半衰期为3.2天，高组织浓度表明，第1天500 mg每日一次，随后250 mg每日一次，持续4天，或每日3次500 mg剂量的拟议标准剂量方案将在各种组织中产生高于3 mg/kg的组织浓度。由于这些组织浓度超过相关病原体的MIC，因此这些给药方案应能有效对抗呼吸道和软组织感染。一个单一的1克剂量可以有效地治疗许多性传播疾病。
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 04 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.