Influence of study design in assessing food effects on absorption of erythromycin base and erythromycin stearate.
We performed a series of six single-dose and multiple-dose studies to evaluate the effect of food on the absorption of erythromycin base and erythromycin stearate. When we used a single-dose design, we found that an unprotected erythromycin base preparation was absorbed extensively if a prolonged fast preceded administration of the drug. A shorter faster period (as occurs in clinical settings) dramatically reduced the absorption of unprotected base; however, 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 to 59% less well absorbed than the enteric-coated base formulation. Furthermore, the enteric-coated base formulation performed equally well when administered either every 6 h between meals (fasting) or four 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.
D000328:Adult; D004917:Erythromycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism*; D005215:Fasting; D005502:Food; D006801:Humans; D007408:Intestinal Absorption; D007700:Kinetics; D012107:Research Design; D013607:Tablets; D013608:Tablets, Enteric-Coated
D013607:Tablets; D013608:Tablets, Enteric-Coated; D004917:Erythromycin; C011462:erythromycin stearate