• The Korean Journal of Pharmacology
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• v.23 no.1
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• pp.1-7
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• 1987

The renal handling and tissue distribution of pyrazinamide were studied after administration of single dose intravenous injection for 15 min or constant infusion in New Zealand White rabbits. Peak pyrazinamide serum concentration ranged from 57.3 to $105.0{\mu}g/ml$ ($mean{\pm}SD;83.0{\pm}17.8$). The mean half-life of the a phase was $0.143{\pm}0.047$ hr while the ${\beta}$ phase ranged from 1.66 to 3.25 hr($mean{\pm}SD;2.38{\pm}0.57$). The mean steady-state volume of distribution in non-compartmental model was $0.935{\pm}0.362\;L/kg$ Excretion ratio of pyrazinamide was dramatically reduced from 1.02 to 0.30 when unbound serum pyrazinamide concentration was increased from 6.04 to $60.9\;{\mu}g/ml$. The urine flow dependency of renal clearance of pyrazinamide was demonstrated in steady-state serum concentration. The tissue/serum concentration ratio of pyrazinamide was highest in kidney and lowest in skeletal muscle among the tissues examined. The results suggested that a large fraction of pyrazinamide filtered by glomerulus and secreted by renal tubule was reabsorbed and this tubular reabsorption of pyrazinamide might be greatly influenced by urine flow.