Binding, distribution and efficacy of erythromycin (author's transl)

Abstract

The significance of the binding of antibiotics in humans in still a controversial question. In principle, only free, unbound antibiotic is considered to be diffusible and biologically active. With unimpaired measurements and a binding balance within the normal therapeutic concentration range, the free portion of erythromycin in the human serum is found to depend significantly on the total concentration of erythromycin. For example, for concentrations of 1, 16 and 24 mg/l, approx. 74%, 54% and 46% are bound (+38 degrees C). binding is temperature-dependent and decreases with decreasing temperature. At +4 degrees C, 44% of 1 mg/l and 30% of 16 mg/l are bound. These binding characteristics are based in part on the properties of erythromycin's major binding partner in the serum - acidic alpha1-glycoprotein. Albumin only contributes slightly to the overall binding and is not concentration-dependent in the therapeutic range, i.e. it cannot be saturated. Binding phenomena have a decisive influence on the distribution of an antibiotic within an organism. In the case of erythromycin, the tissue levels in nearly every organ are higher, sometimes considerably higher, than the corresponding serum levels. We have shown the binding of erythromycin to cytosol and particle fractions in certain organs and compared this to the binding in the serum. The antibacterial principle regarding the efficacy of erythromycin is also based primarily on a binding reaction which maintains the concentration gradient for the intake of erythromycin in microorganisms. The kinetics ofintake (microorganism) are compared to those of binding (macroorganism) and referred to the minimum inhibitory concentration.