Oxidative stress during antituberculous therapy in young and elderly patients.
Using allantoin (ATN) as a marker for reactive oxygen species (ROS), oxidative stress during antituberculous (anti-TB) therapy was compared in 10 young and 9 elderly patients. Before treatment, ATN plasma concentrations in patients were similar to that of volunteers. Administration of a combination of isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA) increased plasma ATN in both groups of patients. ATN concentrations (M +/- SE) at six hours were higher (P < 0.05) in elderly than in young patients on day one, 8.22 +/- 1.50 vs 1.89 +/- 0.98 microgram/mL); day 30, (5.85 +/- 0.82 vs 0.87 +/- 0.57 microgram/mL; and day 90, (4.84 +/- 1.24 vs 0.52 +/- 0.50 microgram/mL). Because total amount of ATN excreted was similar in both groups on the three occasions, more ATN was formed in elderly than young patients. In conclusion, there was more oxidative stress in elderly than young patients. It is thereby suggested that Anti-TB drugs induce formation of ROS and elderly patients are at a greater risk of toxicity probably because of poor antioxidant mechanisms.
Walubo
A
A
Department of Pharmacology, University of Cape Town, Medical School, Observatory, South Africa.
Smith
P J
PJ
Folb
P I
PI
D000328:Adult; D000367:Age Factors; D000368:Aged; D000481:Allantoin / Q000097:blood; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage; D008297:Male; D018384:Oxidative Stress; D011718:Pyrazinamide / Q000008:administration & dosage; D012293:Rifampin / Q000008:administration & dosage; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D013997:Time Factors; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*; D014527:Uric Acid / Q000097:blood
D000995:Antitubercular Agents; D017392:Thiobarbituric Acid Reactive Substances; D014527:Uric Acid; D011718:Pyrazinamide; D000481:Allantoin; D007538:Isoniazid; D012293:Rifampin