Pharmacokinetics of pyrazinamide in children suffering from pulmonary tuberculosis

SETTING: The Paediatric and Clinical Pharmacology unit of Maulana Azad Medi cal 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 tu berculosis. METHODS: Serial blood samples were collected at 0, 1, 2, 3, 4, 12 and 24 ho urs after administration of pyrazinamide in a dose of 35 mg/kg. Serum pyraz inamide levers were analysed by spectrophotometry. RESULTS: The serum concentrations of pyrazinamide were above the minimum in hibitory concentration of 20 mu g/ml of pyrazinamide for Mycobacterium tube rculosis up to 6 hours after drug administration in all the patients, and u p to 12 hours in six patients. The mean peak serum concentration of pyrazin amide was 41.2 +/- 11.8 mu g/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 di stribution 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 3 5 mg/kg were above the minimum inhibitory concentration of pyrazinamide for M. tuberculosis for over 6 hours after drug administration. It appears tha t the absorption and the clearance of pyrazinamide is slower, the eliminati on half life longer and the volume of distribution higher in children compa red with the reported values in the adult population.