IN-VITRO STUDIES OF TEICOPLANIN BINDING TO RAT-TISSUES AND ERYTHROCYTES

Teicoplanin is a large polar antibiotic with a large distribution volu me (V-ss=1.2-2.8 l/kg) despite extensive binding to plasma albumin. To understand this observation, binding of H-3-teicoplanin to 10% rat ti ssue homogenates was determined in vitro by ultracentrifugation in the presence of teicoplanin (1-30 mu g/ml). Binding and efflux from eryth rocytes were also studied. The in vitro total-to-unbound tissue concen tration ratio (K-pu) differed widely but for each tissue was concentra tion independent. Upon correction for the plasma unbound fraction, the re was discrepancy between the in vitro and in vivo tissue-to-plasma c oncentration ratios (K-p), the latter calculated from previously publi shed tissue and plasma concentration-time data using the area method. Moreover, calculation of V-ss from in vitro K-p (8.10 l/kg) overestima ted the in vivo value. These results suggest that in vivo teicoplanin binds to cell membranes and enters some but not all cells, such as ery throcytes. (C) 1998 Elsevier Science B.V.