Serum Protein Binding of Erythromycincand Erythromycin 2'-Propionate Ester

Abstract

Human serum and tissue concentrations are reported after oral administration of erythromycin stearate and propionyl erythromycin lauryl sulfate (erythromycin estolate). About 10% of the erythromycin (I) in serum is unbound to serum proteins, whereas about 1.5% of the activity after propionyl erythromycin (erythromycin 2′-propionate ester) (II) is unbound. The half-lives in serum are 1.2 and 1.6 hr., respectively. The area under the total serum concentration curve of II is about fourfold greater than with I, partly because of the longer half-life of the propionyl ester. The threefold difference remaining after adjustment of the areas for the half-lives is the factor by which total II serum levels are higher due to distribution or absorption. Since the percent of free drug in serum is 7 times greater with erythromycin, the higher total levels with the propionyl ester are more than accounted for by distribution alone. No conclusions about the absolute fraction of the dose that is absorbed can be drawn for either drug. Concentrations of both drugs in tissues are more consistent with the free serum levels than with the total concentrations. Since the free levels of antibiotic are a better index of relative effectiveness, earlier reports indicating that higher total serum concentrations of II are due to more complete absorption and better therapeutic efficacy are questioned.