Foulds G, Johnson R B
Drug Metabolism Department, Pfizer Inc, Groton, CT 06340.
J Antimicrob Chemother. 1993 Jun;31 Suppl E:39-50. doi: 10.1093/jac/31.suppl_e.39.
The unique pharmacokinetics of azithromycin are characterized by high, sustained tissue concentrations. The concentrations of azithromycin were predicted, following various multiple dose regimens, from concentrations in tonsillar, prostatic, and uterine tissues following single oral doses. Following a five-day treatment regimen (500 mg on day 1, followed by 250 mg on days 2-5), or a three-day regimen (500 mg daily for three days), concentrations of azithromycin in tonsillar tissue, representative of respiratory tract tissues, will continuously be greater than the MICs for key target pathogens (Streptococcus pyogenes, Haemophilus influenzae, Staphylococcus aureus) in infections of the respiratory tract for up to 10 days. Since tissue concentrations above the MICs for infecting organisms were correlated with efficacy in animal models of infection, short treatment regimens consisting of once-daily oral administration of azithromycin should be effective in the treatment of a variety of infections. A single 1 g oral dose will provide concentrations in the uterus and prostate, representing urogenital tissues, above the MIC for Chlamydia trachomatis for approximately 10 days. Thus, this regimen should be effective in the treatment of chlamydial infections of the genital tract.
阿奇霉素独特的药代动力学特征是组织浓度高且持续时间长。根据单次口服给药后扁桃体、前列腺和子宫组织中的浓度，预测了各种多剂量给药方案后的阿奇霉素浓度。采用五日治疗方案（第1天500毫克，随后第2至5天每天250毫克）或三日治疗方案（连续三天每天500毫克）后，代表呼吸道组织的扁桃体组织中阿奇霉素浓度在长达10天的时间里将持续高于呼吸道感染中关键目标病原体（化脓性链球菌、流感嗜血杆菌、金黄色葡萄球菌）的最低抑菌浓度（MIC）。由于感染生物体的组织浓度高于MIC与感染动物模型中的疗效相关，因此，每日一次口服阿奇霉素的短疗程治疗方案应能有效治疗多种感染。单次口服1克剂量可使代表泌尿生殖组织的子宫和前列腺中的浓度在约10天内高于沙眼衣原体的MIC。因此，该方案应能有效治疗生殖道衣原体感染。
