Maintenance of therapeutically active levels of isoniazid for prolonged periods in rabbits after a single implant of biodegradable polymer.
METHODS
Poor patient compliance is the serious limiting factor in the chemotherapy of tuberculosis.


OBJECTIVE
To solve this problem we have been developing depot-drug delivery of antimycobacterial drugs. Earlier studies with mice using isoniazid in polylactic-co-glycolic acid (PLGA) co-polymer have shown that a single implant of the polymer could ensure sustained levels of free isoniazid for up to 8 weeks. Similar studies were not undertaken in rabbits.


METHODS
The biodegradable PLGA polymer rods containing isoniazid were implanted on the back of the rabbits under anaesthesia in an isoniazid dose of 90 mg/kg. Concentrations of isoniazid and acetylisoniazid in serum and urine were determined by the high-performance liquid chromatography (HPLC) method at close intervals up to 96 h to study the burst-size, and later at weekly intervals up to 9 weeks to study the sustained levels.


CONCLUSIONS
There was no abnormal release of isoniazid in the earlier periods. Concentrations of isoniazid > or = 0.2 microgram/ml were found both in serum and urine up to 63 days after implant. Urine specimen obtained at 6 weeks after giving the implant inhibited the growth of Mycobacterium tuberculosis in vitro as measured by the radiometric (Bactec) method. These findings in non-rodent animal species confirm the usefulness of the depot-drug delivery method of drug administration and warrant hopes for the successful treatment of tuberculosis avoiding the problem of non-compliance.
Kailasam
S
S
Mycobacteriology Research Laboratories, University of Illinois, Chicago.
Daneluzzi
D
D
Gangadharam
P R
PR
D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D007538:Isoniazid / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019344:Lactic Acid; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011817:Rabbits
D003692:Delayed-Action Preparations; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007538:Isoniazid