Chemotherapeutic activity against murine tuberculosis of once weekly administered drugs (isoniazid and rifampicin) encapsulated in liposomes

Co-administration of isoniazid (INH) and rifampicin (RIF) encapsulated in lung specific stealth liposomes at one third of their recommended doses of 12 and 10 mg/kg b.wt., respectively, exhibited a sustained release of these drugs in plasma (5 days) and lungs, liver and spleen (7 days). At these concentrations, T-max and area under curve (AUC) values of liposomal drugs were more than that observed with free drugs. The elimination constant (Kel) was higher for liposomal INH (-0.034+/-0.008) and RIF (-0.017+/-0.009) compared with free INH (-0.392) and RIF (-0.243). Chemotherapeutic efficacy of once weekly-administered liposomal drugs for 6 weeks reduced the mycobacterial load significantly in lungs, liver and spleen of infected mice compared with untreated animals. (C) 2002 Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved.