Pharmacokinetics of pyrazinamide in children suffering from pulmonary tuberculosis.

SETTING: The Paediatric and Clinical Pharmacology unit of Maulana Azad Medical College and Associated Lok Nayak Hospital, New Delhi, India. OBJECTIVE: The pharmacokinetics of the anti-tuberculosis drug pyrazinamide was evaluated in 10 children aged 6 to 12 years suffering from pulmonary tuberculosis. METHODS: Serial blood samples were collected at 0, 1, 2, 4, 6, 12 and 24 hours after administration of pyrazinamide in a dose of 35 mg/kg. Serum pyrazinamide levels were analysed by spectrophotometry. RESULTS: The serum concentrations of pyrazinamide were above the minimum inhibitory concentration of 20 microg/ml of pyrazinamide for Mycobacterium tuberculosis up to 6 hours after drug administration in all the patients, and up to 12 hours in six patients. The mean peak serum concentration of pyrazinamide was 41.2+/-11.8 microg/ml, and this was attained in (Tmax) 2.9+/-1.7 hours. The elimination half life was 10.9+/-4.5 hours, the volume of distribution 16.1+/-10.9 litres and clearance 20.2+/-16.3 ml/minute. The corresponding mean residence time was 19.9+/-14.6 hours. CONCLUSION: The serum pyrazinamide concentrations achieved with a dose of 35 mg/kg were above the minimum inhibitory concentration of pyrazinamide for M. tuberculosis for over 6 hours after drug administration. It appears that the absorption and the clearance of pyrazinamide is slower, the elimination half life longer and the volume of distribution higher in children compared with the reported values in the adult population.