Comparative pharmacokinetics of azithromycin in serum and white blood cells of healthy subjects receiving a single-dose extended-release regimen versus a 3-day immediate-release regimen
Comparative pharmacokinetics of azithromycin in serum and white blood cells of healthy subjects receiving a single-dose extended-release regimen versus a 3-day immediate-release regimen
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DOI：
10.1128/aac.00852-06
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发表时间：
2007-01-01
影响因子：
4.9
通讯作者：
Sharma, Amarnath
中科院分区：
文献类型：
--
作者：
Liu, Ping;Allaudeen, Hameed;Sharma, Amarnath
在24名健康成人受试者中进行的一项开放标签、随机、平行组研究中，通过血清和白色血细胞（WBC）来表征阿奇霉素单次给药方案（2.0 g缓释微球）的药代动力学特征，并与3天方案（500 mg速释片剂，每日一次;总剂量1.5 g）进行比较。两种方案开始给药后5天内采集连续血样。在整个研究期间进行安全性评估。与3天给药方案相比，2.0 g阿奇霉素微球单次给药在开始给药后的前24小时内血清和WBC中的暴露量显著更高：从时间0至给药后24小时的曲线下面积（AUC（0-24））约为3倍，第1天的平均峰浓度约为2倍。单次给药方案提供的血清和WBC中的阿奇霉素总暴露量与3天给药方案相似，如血清和WBC（单核白细胞[MNL]和多形核白细胞[PMNL]）中的AUC（0-120）和阿奇霉素谷浓度相似所证明。对于这两种治疗方案，MNL和PMNL中的平均总阿奇霉素暴露量分别比血清中高约300倍和600倍。两种方案开始给药后，MNL和PMNL中的阿奇霉素浓度保持在10 μ g/ml以上至少5天。通过缓释微球制剂安全地实现了第一天剂量的这种“前负荷”，其在细菌负荷可能最高时使药物暴露最大化。
The pharmacokinetic profiles of azithromycin given as a single-dose regimen (2.0-g extended-release microspheres) were characterized in serum and white blood cells (WBC) and compared with those of a 3-day regimen (a 500-mg immediate-release tablet once daily; total dose, 1.5 g) in an open-label, randomized, parallel-group study of 24 healthy adult subjects. Serial blood samples were collected up to 5 days after the start of dosing for both regimens. Safety assessments were conducted throughout the study. A single 2.0-g dose of azithromycin microspheres achieved significantly higher exposures in serum and WBC during the first 24 h after the start of dosing than a 3-day regimen: an approximately threefold higher area under the curve from time zero to 24 h postdose (AUC(0-24)) and an approximately twofold higher mean peak concentration on day 1. The single-dose regimen provided total azithromycin exposures in serum and WBC similar to those of the 3-day regimen, as evidenced by the similar AUC(0-120) and trough azithromycin concentrations in serum and WBC (mononuclear leukocytes [MNL] and polymorphonuclear leukocytes [PMNL]). For both regimens, the average total azithromycin exposures in MNL and PMNL were approximately 300- and 600-fold higher than those in serum. Azithromycin concentrations in MNL and PMNL remained above 10 mu g/ml for at least 5 days after the start of dosing for both regimens. This "front-loading" of the dose on day I is safely achieved by the extended-release microsphere formulation, which maximizes the drug exposure at the time when the bacterial burden is likely to be highest.