Pharmacokinetics of pyrazinamide and its metabolites in healthy subjects
Identifieur interne : 000266 ( Istex/Curation ); précédent : 000265; suivant : 000267Pharmacokinetics of pyrazinamide and its metabolites in healthy subjects
Auteurs : C. Lacroix [France] ; T. Phan Hoang [France] ; J. Nouveau [France] ; C. Guyonnaud [France] ; G. Laine [France] ; H. Duwoos [France] ; O. Lafont [France]Source :
- European Journal of Clinical Pharmacology [ 0031-6970 ] ; 1989-07-01.
Abstract
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).
Url:
DOI: 10.1007/BF00558302
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Lacroix</name><affiliation wicri:level="1"><mods:affiliation>Departments of Pharmacokinetics and Pneumology, Centre Hospitalier Général, Le Havre, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Departments of Pharmacokinetics and Pneumology, Centre Hospitalier Général, Le Havre</wicri:regionArea></affiliation></author><author><name sortKey="Phan Hoang, T" sort="Phan Hoang, T" uniqKey="Phan Hoang T" first="T." last="Phan Hoang">T. Phan Hoang</name><affiliation wicri:level="1"><mods:affiliation>Departments of Pharmacokinetics and Pneumology, Centre Hospitalier Général, Le Havre, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Departments of Pharmacokinetics and Pneumology, Centre Hospitalier Général, Le Havre</wicri:regionArea></affiliation></author><author><name sortKey="Nouveau, J" sort="Nouveau, J" uniqKey="Nouveau J" first="J." last="Nouveau">J. 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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).</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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