Serum and WBC pharmacokinetics of 1500 mg of azithromycin when given either as a single dose or over a 3 day period in healthy volunteers
Serum and WBC pharmacokinetics of 1500 mg of azithromycin when given either as a single dose or over a 3 day period in healthy volunteers
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DOI：
10.1093/jac/47.1.61
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发表时间：
2001-01-01
影响因子：
5.2
通讯作者：
Gray, CL
中科院分区：
文献类型：
--
作者：
Amsden, GW;Gray, CL
由于阿奇霉素的半衰期较长，因此正在研究越来越短的剂量方案来治疗呼吸道感染。先前的研究得出结论，3 天和 5 天（总共 1.5 g）方案不仅提供至少相等的血清和 WBC 暴露，而且还提供相等的有效率。一项较早的临床研究对非典型肺炎患者使用一次性 1.5 克完整剂量或当前的 3 天治疗方案，结果显示具有相同的疗效。目前正在成人和儿童人群中进行类似的试验。本研究的目的是调查当阿奇霉素按照当前的 3 天治疗方案或单次大剂量给药时，血清和白细胞暴露是否相等。同等暴露将有助于验证单剂量方案的未来临床试验。 12 名健康志愿者随机接受两种阿奇霉素治疗方案（单剂量 1.5 克，每天 500 毫克，持续 3 天）。在基线时收集血清和白细胞样本，并在每个方案首次给药后 10 天内重复收集。血清样品通过 HPLC 进行测定（CV% < 10），WBC 样品通过液相色谱/质谱法进行测定（CV% < 10）。使用非房室方法对数据进行建模。通过方差分析进行统计，显着性定义为 P < 0.05。所有受试者均完成了两种治疗方案，且不良反应发生率极低。血清数据[平均值（范围）]表明两种方案之间的暴露没有显着差异[单次13.1（3.02-20.6）mgh/L与3天11.2（2.98-24.5）mg.h/L：P = 0.12]，尽管它倾向于较短的方案。白细胞结果显示暴露量比血清高得多，但两种方案之间没有发现显着差异。这些结果表明，单次口服 1.5 g 阿奇霉素治疗呼吸道感染的方案应提供至少等于目前批准的治疗方案的暴露量。
Owing to azithromycin's prolonged half-life, shorter and shorter dosage regimens are being studied for treatment of respiratory tract infections. Previous studies have concluded that the 3 and 5 day (1.5 g total) regimens not only provide at least equal serum and WBC exposures but also equal efficacy rates. An earlier clinical study using the entire 1.5 g dose at once or the current 3 day regimen in patients with atypical pneumonia noted equal efficacy. Similar trials are currently underway In both adult and paediatric populations. The goal of the present study was to investigate whether there were equal serum and WBC exposures when azithromycin was dosed as the current 3 day regimen or as a single large dose. Equal exposures would help validate future clinical trials of single dose regimens. Twelve healthy volunteers received both azithromycin regimens (1.5 g single dose and 500 mg/day for 3 days) in random order. Serum and WBC samples were collected at baseline and repeatedly for 10 days following the first dose of each regimen. Serum samples were assayed via HPLC (CV% < 10) and WBC samples via liquid chromatography/mass spectrometry (CV% < 10). Data were modelled using noncompartmental methods. Statistics were via ANOVA with significance defined as P < 0.05. All subjects completed both regimens with minimal incidence of adverse effects. Serum data [mean (range)] demonstrated no significant difference in exposure between the two regimens [single 13.1 (3.02-20.6) mgh/L versus 3 day 11.2 (2.98-24.5) mg .h/L: P = 0.12], although it favoured the shorter regimen. WBC results demonstrated much higher exposures than seen with serum, but no significant difference between the two regimens was identified. These results suggest that a single oral 1.5 g regimen of azithromycin for respiratory tract infections should provide exposure at least equal to currently approved treatment regimens.