Plasma protein binding of gyrase inhibitors

Plasma protein binding of a wide range of gyrase inhibitors in clinical practice or trials has been determined by ultrafiltration to determine structure-protein binding relationships. The protein binding was independent of overall lipophilicity. In particular, the "western" pari of the "quinolone" skeleton, consisting of a heterocyclus at position 7 and varying substituents at position 8, strongly influences the extent of protein binding, indicating that this part interacts with the plasma protein. In contrast, substituents in position N-1 do not show an effect on the protein binding in this series of compounds.