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Pharmacokinetics of isoniazid in pulmonary tuberculosis--a comparative study at two dose levels
Insights
A lower dose of isoniazid (5 mg/kg) is effective for treating childhood pulmonary tuberculosis. This dosage, combined with other drugs, showed comparable pharmacokinetic parameters and clinical outcomes to a higher dose.
Area of Science:
- Pediatric infectious diseases
- Pharmacology and pharmacokinetics
- Tuberculosis treatment
Background:
- Pediatric tuberculosis requires effective and safe treatment regimens.
- Optimizing drug dosages is crucial for efficacy and minimizing adverse effects in children.
Purpose of the Study:
- To compare the pharmacokinetic profiles and clinical effectiveness of two different isoniazid dosages (10 mg/kg vs. 5 mg/kg) in children with pulmonary tuberculosis.
Main Methods:
- A randomized, open-label, controlled trial involving 20 children (6-12 years) with pulmonary tuberculosis.
- Administered a three-drug regimen including rifampicin, pyrazinamide, and isoniazid (10 mg/kg or 5 mg/kg) for 14 days.
- Monitored serum isoniazid concentrations and clinical outcomes over a 6-month follow-up period.
Main Results:
- Serum isoniazid concentrations remained within therapeutic ranges at 6 and 24 hours post-administration in both dosage groups.
- Key pharmacokinetic parameters, including half-life and clearance, were comparable between the 10 mg/kg and 5 mg/kg isoniazid groups.
- All children demonstrated similar clinical and radiological improvements after 6 months of treatment.
Conclusions:
- Isoniazid at 5 mg/kg, when used in combination with rifampicin and pyrazinamide, is adequate for treating pulmonary tuberculosis in children.
- The lower isoniazid dosage demonstrates comparable efficacy and pharmacokinetic behavior to the higher dose, suggesting potential for optimized pediatric TB treatment.
Objectives:
To compare the pharmacokinetic parameters and the clinical efficacy of isoniazid, administered in 10 mg/kg or 5 mg/kg to children suffering from pulmonary tuberculosis.
Design:
A randomized, open, controlled clinical trial.
Setting:
Teaching hospital in New Delhi.
Subjects:
Twenty children suffering from pulmonary tuberculosis in the age group 6-12 years.
Interventions:
A three drug antitubercular regimen comprising of rifampicin (10 mg/kg), pyrazinamide (30 mg/kg) and isoniazid in a dose of either 10 mg/kg (Group I) or 5 mg/kg (Group II) was administered for fourteen days. On day fifteen serial blood samples were collected at 0,1,2,3,6 and 24 h of isoniazid administration and analyzed spectrofluorometrically.
Main Outcome Measures:
Serum isoniazid concentrations and clinical response in both the groups.
Results:
In both the groups, serum concentration of isoniazid were above the therapeutic range (0.5-2 micrograms/ml) at 6 h following drug administration. The minimum serum concentration of isoniazid was within or above minimum inhibitory concentration of the drug at 24 h in both the groups. The time to achieve maximum serum concentration, elimination half life, elimination rate constant, mean residence time, volume of distribution at steady state and plasma drug clearance were also comparable. At the end of 6 months follow up, all children showed comparable clinical and radiological improvement.
Conclusion:
Isoniazid in a dose of 5 mg/kg administered with other antitubercular drugs appears adequate for treatment of pulmonary tuberculosis in children.