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Isoniazid and acetylisoniazid kinetics in serum and urine in pulmonary primary complex with intermittent regimen
1Department of Pediatrics, All India Institute of Medical Sciences, New Delhi.
Insights
This study measured isoniazid and acetylisoniazid levels in children with pulmonary primary complex on an intermittent regimen. Results show peak drug concentrations and half-life, informing pediatric tuberculosis treatment.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Pediatric Infectious Diseases
- Tuberculosis Treatment
Background:
- Pediatric primary tuberculosis requires effective and safe treatment regimens.
- Understanding drug concentrations is crucial for optimizing intermittent therapy in children.
- Isoniazid (INH) and acetylisoniazid (AcINH) are key metabolites in tuberculosis treatment.
Purpose of the Study:
- To investigate serum and urine concentrations of isoniazid (INH) and acetylisoniazid (AcINH) in pediatric patients with pulmonary primary complex (PPC).
- To evaluate drug pharmacokinetics during an intermittent treatment regimen (2HR, 4H2R2) in children.
- To determine peak concentrations, time to peak, and half-life of INH and AcINH.
Main Methods:
- Twenty pediatric patients (1-13 years) with PPC received an intermittent regimen of INH and rifampicin.
- Serum and urine samples were collected at specific intervals during the biweekly phase of treatment.
- High-performance liquid chromatography (HPLC) was used to quantify INH and AcINH concentrations.
Main Results:
- Peak serum concentrations (Cmax) for INH and AcINH were 2.6 ± 1.8 and 5.5 ± 2.6 µg/ml, respectively.
- Peak urine concentrations for INH and AcINH were 5.7 ± 4.8 and 21.5 ± 12.1 mg, respectively.
- The half-life (T1/2) of INH was 4.5 hours, with a pre-dose concentration of 0.47 ± 0.3 µg/ml in the biweekly phase.
Conclusions:
- The study provides pharmacokinetic data for isoniazid and acetylisoniazid in children with PPC on intermittent therapy.
- These findings can aid in refining dosing strategies for pediatric tuberculosis treatment.
- Understanding drug levels is essential for ensuring treatment efficacy and safety in young patients.
Abstract:
Twenty patients, 1 through 13 years of age from Pediatric Tuberculosis Clinic of All India Institute of Medical Sciences, New Delhi, suffering from pulmonary primary complex (PPC) were investigated for serum and urine concentrations of isoniazid (INH) and acetylisoniazid (AcINH). Patients were put on an intermittent regimen - 2HR, 4H2R2, INH (H) was given in a dose of 10 mg/kg/day for first 2 months (the daily dose phase), followed by 20 mg/kg/dose in biweekly phase of regimen for rest of the 4 months, whereas, rifampicin (R) was given as 12 mg/kg in both daily as well as biweekly phases. In the biweekly phase of regimen, after 7 days of biweekly administration of drugs, INH and AcINH concentrations were estimated by HPLC at 0,1,3,5 and 7 hours in serum, and at 0-3, 3-6, 6-12 and 12-24 hour-intervals of drug administration in urine. Peak concentrations of INH and AcINH (Mean +/- SD) were 2.6 +/- 1.8 and 5.5 +/- 2.6 micrograms/ml in serum (Cmax), and 5.7 +/- 4.8 and 21.5 +/- 12.1 mg in urine, respectively. Time to achieve Cmax (Tmax), for INH and AcINH were 1 and 5 hours respectively while time of peak concentration in urine for INH was 3-6 hours and for AcINH 6-12 hours. The half-life (T1/2) of INH was 4.5 hours and area under serum-concentration time-curve (AUC0-7h) was 20.7 micrograms/ml/h (mean values). In biweekly phase (4H2R2) of regimen, just before administration of next dose, 0 hour (or 72 hours) concentration of INH was estimated at 0.47 +/- 0.3 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)
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