Randinitis E J, Sedman A J, Welling P G, Kinkel A W
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
J Clin Pharmacol. 1989 Jan;29(1):79-84. doi: 10.1002/j.1552-4604.1989.tb03241.x.
The effect of food on the relative bioavailability of an erythromycin particles-in-tablet formulation was studied in 27 healthy volunteers, using a four-way, crossover study design with the following treatments: one or two erythromycin capsules USP (Eryc, Parke-Davis), or one polymer-coated erythromycin particles-in-tablet (PCE, Abbott) administered fasting or with a high-fat meal. Under fasting conditions the erythromycin particles-in-tablet and erythromycin capsule formulations are bioequivalent based on similar tmax and dose-normalized Cmax and AUC values. The rate and extent of absorption from the particles-in-tablet formulation, however, are dramatically reduced following administration with a meal. Mean Cmax and AUC values decreased by 73% and 72%, respectively, and seven subjects had no detectable erythromycin plasma concentrations for 16 hours following administration of the particles-in-tablet formulation with the high-fat meal. Greater than 40% of the subjects had nonfasting Cmax and AUC values that were less than 10% of those values following administration of the dose fasting. Cmax and AUC values in nonfasting subjects were within 75% to 125% of fasting values in only two and one of 27 subjects, respectively. The erythromycin particles-in-tablet formulation therefore should not be administered with meals.
在27名健康志愿者中，采用四交叉研究设计，研究了食物对红霉素片制剂相对生物利用度的影响，具体治疗方案如下：空腹或高脂饮食时服用1粒或2粒红霉素USP胶囊（Eryc，Parke-Davis公司），或1片聚合物包衣的红霉素片制剂（PCE，雅培公司）。在空腹条件下，基于相似的达峰时间（tmax）、剂量标准化的峰浓度（Cmax）和药时曲线下面积（AUC）值，红霉素片制剂和红霉素胶囊制剂具有生物等效性。然而，进食后，片制剂中红霉素的吸收速率和程度显著降低。服用高脂饮食后的片制剂后，平均Cmax和AUC值分别下降了73%和72%，7名受试者在服药后16小时内未检测到红霉素血浆浓度。超过40%的受试者非空腹状态下的Cmax和AUC值低于空腹服药后相应值的10%。在27名受试者中，分别只有2名和1名非空腹受试者的Cmax和AUC值在空腹值的75%至125%范围内。因此，红霉素片制剂不应与食物同服。
