[From serum pharmacokinetics to extravascular pharmacokinetics of antibiotics. Importance of protein binding].

Serum and urinary concentrations of antibiotics are not predictive of their extravascular distribution. Data from an animal model giving access to an extravascular fluid have demonstrated the effects of protein binding on the extravascular diffusion of cephalosporins. A high percentage of protein binding delays extravascular distribution and facilitates accumulation from repeated doses. Moreover, strongly bound drugs may reduce the number of protein-bound cephalosporin molecules by competing for binding sites and interfere with the extravascular distribution of these antibiotics without modifying their serum levels.