Effect of food on absorption and hydrolysis of erythromycin acistrate

Abstract

Effect of food on absorption of erythromycin acistrate (2'-acetyl erythromycin stearate, Erasis; CAS 96128-89-1) was studied in 14 healthy volunteers in a randomized cross-over design. The subjects were given 400 mg erythromycin acistrate enteric coated tablets b.i.d. for 4 days. On the 1st and 4th days the tablets were taken after an overnight fast or immediately after a light or a heavy breakfast. Erythromycin (E), 2'-acetyl-erythromycin (2AE), anhydroerythromycin and anhydro-2'-acetyl-erythromycin concentrations in plasma were analyzed chemically by HPLC. After a single dose the lag time of absorption (tlag) was significantly longer after both types of breakfasts as compared to fast. The tmax of E and 2AE were also somewhat delayed by food although tmax of 2AE after a heavy breakfast only differed statistically significantly from that of the fasting state. Food significantly delayed the absorption especially in some subjects since no drug was observed during the 12-h observation period in 2 and 5 of the subjects after a light and heavy breakfast, respectively. At steady state the delaying effect of food on absorption had almost disappeared. No significant differences were observed in Cmax- or AUC0-12-values between the fasting and the fed states both after a single dose or at steady state. It is concluded, that food does not affect the mean bioavailability of erythromycin acistrate neither the mean rate of absorption but in some subjects the absorption from enteric coated tablets might be significantly delayed.