Pharmacokinetics of pyrazinamide in children with primary progressive disease of lungs.

ABSTRACT

Background & objectives: As the dosages recommended for children are based on weight, empirical and derived by extrapolation from the studies in adults, pyrazinamide (PZA) pharmacokinetics in children is likely to be different from adults. Limited information exists regarding the pharmacokinetics of PZA in paediatric patients of primary progressive disease (PPD) of lungs. This study aims to look at the changed pharmacokinetics of pyrazinamide in children with PPD of lungs by using reverse phase high-pressure liquid chromatography (HPLC). Methods: A total of 40 children (age range 5 to 13 yr) of PPD were receiving pyrazinamide (30 mg/kg/day). On 11th day of short course antitubercular therapy, blood samples (two per day from 11th to 13th day) were collected at 0 h (pre-dose), 1, 2, 3, 4, 8 and 24 h after pyrazinamide administration and concentration of pyrazinamide was estimated by reverse phase high-pressure liquid chromatography. The mean peak serum concentration, the time to reach mean peak serum concentration, total clearance, concentration at time zero, volume of distribution, terminal elimination rate constant, elimination half-life, total area under serum concentration-time curve were measured. Results: The mean serum concentrations of pyrazinamide were found higher than its minimum inhibitory concentration (20 μg/ml) required to inhibit the growth of tubercle bacilli from 1 to 8 h continuously. Interpretation & conclusions: Our results suggest that a dose of 30 mg/kg/day achieves much higher concentration of pyrazinamide as compared to its minimum inhibitory concentration (20 μg/ml). Therefore, lowering of pyrazinamide dosage is suggested in children for better patient compliance along with reduction in cost, side-effects and toxicity without compromising its efficacy.