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.
Labana
Sumeet
S
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, 160 012, Chandigarh, India.
Pandey
Rajesh
R
Sharma
Sadhna
S
Khuller
G K
GK
D000818:Animals; D000904:Antibiotics, Antitubercular / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D000995:Antitubercular Agents / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D005260:Female; D007538:Isoniazid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D008081:Liposomes / Q000493:pharmacokinetics; D008168:Lung / Q000378:metabolism*; D008297:Male; D051379:Mice; D009169:Mycobacterium tuberculosis; D012293:Rifampin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D012680:Sensitivity and Specificity; D014376:Tuberculosis / Q000188:drug therapy*
D000904:Antibiotics, Antitubercular; D000995:Antitubercular Agents; D004337:Drug Carriers; D008081:Liposomes; D007538:Isoniazid; D012293:Rifampin