INFLUENCE OF STUDY DESIGN IN ASSESSING FOOD EFFECTS ON ABSORPTION OF ERYTHROMYCIN BASE AND ERYTHROMYCIN STEARATE
INFLUENCE OF STUDY DESIGN IN ASSESSING FOOD EFFECTS ON ABSORPTION OF ERYTHROMYCIN BASE AND ERYTHROMYCIN STEARATE
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DOI：
10.1128/aac.20.2.190
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发表时间：
1981-01-01
影响因子：
4.9
通讯作者：
CHODOS, DJ
中科院分区：
文献类型：
--
作者：
DISANTO, AR;CHODOS, DJ
进行了一系列6次单次给药和多次给药研究，以评价食物对红霉素碱和硬脂酸红霉素吸收的影响。当使用单次给药设计时，如果在给药前长时间禁食，则无保护的红霉素基础制剂被广泛吸收。较短的禁食期（如临床环境中发生的）显著降低了未保护碱的吸收;当通过单次给药检测程序进行评价时，薄膜包衣片似乎与肠溶包衣片一样具有良好的保护作用，并且吸收更快。相反，当市售红霉素基质薄膜包衣制剂在两餐（空腹）之间以多剂量方式进行评价时，药物的吸收比市售肠溶包衣基质片剂低约25%。最后，当市售薄膜包衣红霉素基质和硬脂酸盐制剂随餐给药时，两种薄膜包衣制剂的吸收均比肠溶包衣基质制剂低43-59%。肠溶包衣基质制剂在餐间每6小时（空腹）或每天4次（餐后立即和睡前）给药时表现同样良好。这些研究证明了在评价酸不稳定药物的生物利用度时需要多剂量生物利用度技术。
A series of 6 single-dose and multiple-dose studies was performed to evaluate the effect of food on the absorption of erythromycin base and erythromycin stearate. When a single-dose design was used, an unprotected erythromycin base preparation was absorbed extensively if a prolonged fast preceded administration of the drug. A shorter fasting period (as occurs in clinical settings) dramatically reduced the absorption of unprotected base; film-coated tablets seemed to be as well protected as and were absorbed more rapidly than enteric-coated tablets when they were evaluated by single-dose testing procedures. In contrast, when a commercially available film-coated preparation of erythromycin base was evaluated in multidose fashion between meals (fasting), the drug was about 25% less well absorbed than commercially available enteric-coated base tablets. Finally, when commercially available film-coated erythromycin base and stearate formulations were administered with meals, both film-coated preparations were 43-59% less well absorbed than the enteric-coated base formulation. The enteric-coated base formulation performed equally well when administered either every 6 h between meals (fasting) or 4 times a day (immediately after meals and at bedtime). These studies document the need for multidose bioavailability techniques when the bioavailabilities of acid-labile drugs are evaluated.