Urinary pharmacokinetics of pyrazinamide in pediatric patients with primary progressive disease of lungs

In present study we aimed to characterize the pharmacokinetics of pyrazinamide in Indian children patients with primary progressive disease of lungs. Dosages for children are based on weight and extrapolated from the data from studies with adults. However, pharmacokinetics for children, especially young children, is likely to be different from that of adults. A total forty pediatric patients in the age range of 5 to 13 yrs were recruited on the basis of strict exclusion and inclusion criteria. Pyrazinamide dose calculated as 30-mg/kg/day bodyweight along with other anti-tubercular drugs were given. Over a 24 h period urine samples were collected at 0-3, 3-6, 6-12 and 12-24 h intervals of pyrazinamide administration. Volume of urine samples collected at different time intervals was measured and 3 mL of urine samples from each time interval was used for estimation of pyrazinamide amount in the urine. A fully validated, reverse phase high-performance liquid chromatography (RP-HPLC) method with UV detection was applied to determine the pyrazinamide concentration in urine samples. In urine samples, total amount and percentage of pyrazinamide excreted was determined at 0-3, 3-6, 6-12 and 12-24 h. Total amount of pyrazinamide and percentage of total oral dose of pyrazinamide excreted in urine in 24 h were estimated. The maximum total concentration excreted (11.51 mg) constituting 31% of the total 24-h amount excreted was seen at 12-24 h interval indicating its delayed excretion. Present study findings conclude that significant amount of pyrazinamide is detectable in urine in children patients with primary progressive disease and follow a delayed excretion kinetic pattern.