Blood Levels of Pyrazinamide in Children at Doses Administered Under the Revised National Tuberculosis Control Program.

ABSTRACT

Objectives: To evaluate the blood levels, pharma-cokinetics and pharmacodynamic indices of pyrazinamide (PZA) in children suffering from tuberculosis, at doses administered under the weight band system of Revised National Tuberculosis Control Program of India (RNTCP) of India. Design: Prospective, open-label, non-randomized single-dose study. Setting: 20 children in the age group 5-12 years attending outpatient tuberculosis clinic of a tertiary hospital. Outcome Measures: Blood levels of pyrazinamide after single dose administration, as per the weight band system of RNTCP. Results: Group I (n=7) included children who received pyrazinamide within the recommended 30-35 mg/kg dose (mean 31.9+0.8 mg/kg) and Group II (n=13) included those who received a dose lower than 30 -35 mg/kg (mean 28.1±0.3 mg/ kg). The Cmax (95% CI of difference 2.2, 13.2; P=0.008) and AUC (95% CI of difference 28.6, 208.1; P=0.01) were significantly lower in Group II. The duration of time for which the concentration was maintained above 25 μg ml-1 was 4-8 h in Group I and 3-5.5 h in Group II (95% CI of difference 0.1, 2.0; P=0.03). The half life, elimination rate constant, clearance and volume of distribution were comparable in the two groups. The ratios of Cmax and AUC to MIC (25 μg ml-1) in children were lower than that recommended for PZA in adults. Conclusions: Lower blood concentrations are being attained in children receiving PZA doses under the existing weight band system of RNTCP of India. The weight bands may need to be revised and dose recommendations be based on pharmacokinetic and efficacy data in children.