In vitro studies of teicoplanin binding to rat tissues and erythrocytes

Teicoplanin is a large polar antibiotic with a large distribution volume (Vss = 1.2-2.8 l/kg) despite extensive binding to plasma albumin. To understand this observation, binding of 3H-teicoplanin to 10% rat tissue homogenates was determined in vitro by ultracentrifugation in the presence of teicoplanin (1-30 microg/ml). Binding and efflux from erythrocytes were also studied. The in vitro total-to-unbound tissue concentration ratio (Kpu) differed widely but for each tissue was concentration independent. Upon correction for the plasma unbound fraction, there was discrepancy between the in vitro and in vivo tissue-to-plasma concentration ratios (KP), the latter calculated from previously published tissue and plasma concentration-time data using the area method. Moreover, calculation of Vss from in vitro Kp (8.10 l/kg) overestimated the in vivo value. These results suggest that in vivo teicoplanin binds to cell membranes and enters some but not all cells, such as erythrocytes.