Chemotherapy of tuberculosis in mice using single implants of isoniazid and pyrazinamide.
OBJECTIVE
To establish the chemotherapeutic value of a depot drug preparation of isoniazid and pyrazinamide against experimental tuberculosis.


METHODS
To see whether sustained levels of pyrazinamide are available for prolonged periods after a single subcutaneous administration of a biodegradable polylactic-glycolic acid (PLGA) polymer containing the drug, studies were done to ascertain whether a single administration of isoniazid and pyrazinamide in separate PLGA polymers could offer chemotherapeutic protection against a heavy intravenous challenge of susceptible mice with a virulent strain of Mycobacterium tuberculosis similar to that rendered by daily administration of the two drugs for 8 weeks.


RESULTS
Even with three times the daily dose of pyrazinamide contained in the single PLGA polymer implant, no abnormally high (burst) levels of the drug were evident after administration, but sustained levels of the drug were seen up to 54 days. The chemotherapeutic activity of the single PLGA polymer implants was similar to that obtained with standard oral treatment with the two drugs given daily for the entire 8 weeks, as judged by mortality and colony forming unit (CFU) counts of tubercle bacilli from lungs and spleen.


CONCLUSIONS
Treatment with single implants of the PLGA polymer containing anti-mycobacterial drugs offers a strong possibility of circumventing the compliance problem.
Gangadharam
P R
PR
Department of Medicine, University of Illinois at Chicago, 60612, USA. PRGanga@uic.edu
Geeta
N
N
Hsu
Y Y
YY
Wise
D L
DL
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001672:Biocompatible Materials / Q000008:administration & dosage; D001682:Biological Availability; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004343:Drug Implants; D007538:Isoniazid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019344:Lactic Acid / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011100:Polyglycolic Acid / Q000008:administration & dosage; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage; D011718:Pyrazinamide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012680:Sensitivity and Specificity; D014376:Tuberculosis / Q000188:drug therapy*
D000995:Antitubercular Agents; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D004343:Drug Implants; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D011718:Pyrazinamide; D019344:Lactic Acid; D007538:Isoniazid