Summary
The plasma and urine pharmacokinetic parameters of pyrazinamide and of its metabolites (pyrazinoic acid, 5-hydroxy-pyrazinamide, 5-hydroxy-pyrazinoic acid and pyrazinuric acid) have been studied after a single oral dose of pyrazinamide 27 mg · kg−1 in 9 healthy subjects.
Pyrazinamide was rapidly absorbed (tmax ≤1 h) and showed a short distribution phase followed by an elimination phase of t1/2β=9.6 h. The close similarity of the apparent elimination rates of the metabolites led to a second trial of a single oral dose of pyrazinoic acid to evaluate the formation and elimination stages.
The limiting factor was found to be the activity of a microsomal deamidase (pyrazinoic acid formation from pyrazinamide and 5-hydroxy-pyrazinoic acid formation from 5-hydroxy-pyrazinamide). In contrast, oxidation by xanthine oxidase occurred very rapidly (5-hydroxy-pyrazinamide formation and pyrazinoic acid catabolism to 5-hydroxy-pyrazinoic acid).
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Lacroix, C., Phan Hoang, T., Nouveau, J. et al. Pharmacokinetics of pyrazinamide and its metabolites in healthy subjects. Eur J Clin Pharmacol 36, 395–400 (1989). https://doi.org/10.1007/BF00558302
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DOI: https://doi.org/10.1007/BF00558302