Antituberculosis Activity and Pharmacokinetics of Polymer Conjugates of Isoniazid and Ethambutol

Aconjugate containing isonicotinic acid hydrazide linked with a hydrazone bond (20 ± 2 mol%) and ionically bonded ethambutol (25 ± 2 mol%) was prepared by reacting a dialdehyde derivative of poly(galacturonic acid) successively with isonicotinic acid hydrazide and ethambutol. The obtained conjugate showed pronounced antituberculosis activity in vitro on clinical strains of M. tuberculosis and H37Rv and in vivo on Humanis and Bovis strains. The therapeutic concentrations of the active substances (isoniazid and ethambutol) in blood after administration of the conjugate to rats persisted longer than those of their low-molecular-mass analogs, thereby exhibiting a prolonged antituberculosis effect.