Pharmacokinetics of pyrazinamide and its metabolites in patients with hepatic cirrhotic insufficiency.
Identifieur interne : 000347 ( Ncbi/Checkpoint ); précédent : 000346; suivant : 000348Pharmacokinetics of pyrazinamide and its metabolites in patients with hepatic cirrhotic insufficiency.
Auteurs : C. Lacroix [France] ; J L Tranvouez ; T. Phan Hoang ; H. Duwoos ; O. LafontSource :
- Arzneimittel-Forschung [ 0004-4172 ] ; 1990.
English descriptors
- KwdEn :
- MESH :
- chemical , analogs & derivatives : Pyrazinamide.
- chemical , blood : Pyrazinamide.
- metabolism : Liver Cirrhosis, Pyrazinamide.
- chemical , pharmacokinetics : Pyrazinamide.
- Adult, Chromatography, High Pressure Liquid, Female, Half-Life, Humans, Liver Function Tests, Male.
Abstract
The pharmacokinetics of pyrazinamide (Pirilène) and its metabolites are evaluated in ten subjects with hepatic insufficiency, after an oral dose of 19.3 +/- 0.6 mg.kg-1 and the results are compared to those of a group of nine healthy subjects (control group). The results exhibit a marked reduction of the pyrazinamide total clearance (0.48 vs 0.84 ml.min-1.kg-1) and an increase in half-life from 9.19 h to 15.07 h in the patients group. The area under the curve of pyrazinoic acid (the main metabolite) is increased from 97 to 280 mg.h.l-1 with a half-life twice as much as that of the control group. The hepatic insufficiency entails a marked reduction of the common posology as well as a closer survey of the biologic hepatic parameters and of uric acid the renal elimination of which is inhibited by pyrazinoic acid.
PubMed: 2340003
Affiliations:
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pubmed:2340003Le document en format XML
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<author><name sortKey="Lacroix, C" sort="Lacroix, C" uniqKey="Lacroix C" first="C" last="Lacroix">C. Lacroix</name>
<affiliation wicri:level="1"><nlm:affiliation>Unité de Pharmacocinétique, Centre Hospitalier Général, Le Havre, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Unité de Pharmacocinétique, Centre Hospitalier Général, Le Havre</wicri:regionArea>
<placeName><settlement type="city">Le Havre</settlement>
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<author><name sortKey="Tranvouez, J L" sort="Tranvouez, J L" uniqKey="Tranvouez J" first="J L" last="Tranvouez">J L Tranvouez</name>
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<author><name sortKey="Phan Hoang, T" sort="Phan Hoang, T" uniqKey="Phan Hoang T" first="T" last="Phan Hoang">T. Phan Hoang</name>
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<author><name sortKey="Duwoos, H" sort="Duwoos, H" uniqKey="Duwoos H" first="H" last="Duwoos">H. Duwoos</name>
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<author><name sortKey="Lafont, O" sort="Lafont, O" uniqKey="Lafont O" first="O" last="Lafont">O. Lafont</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Pharmacokinetics of pyrazinamide and its metabolites in patients with hepatic cirrhotic insufficiency.</title>
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<author><name sortKey="Phan Hoang, T" sort="Phan Hoang, T" uniqKey="Phan Hoang T" first="T" last="Phan Hoang">T. Phan Hoang</name>
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<author><name sortKey="Duwoos, H" sort="Duwoos, H" uniqKey="Duwoos H" first="H" last="Duwoos">H. Duwoos</name>
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<author><name sortKey="Lafont, O" sort="Lafont, O" uniqKey="Lafont O" first="O" last="Lafont">O. Lafont</name>
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<series><title level="j">Arzneimittel-Forschung</title>
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<term>Humans</term>
<term>Liver Cirrhosis (metabolism)</term>
<term>Liver Function Tests</term>
<term>Male</term>
<term>Pyrazinamide (analogs & derivatives)</term>
<term>Pyrazinamide (blood)</term>
<term>Pyrazinamide (metabolism)</term>
<term>Pyrazinamide (pharmacokinetics)</term>
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<keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Pyrazinamide</term>
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<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Pyrazinamide</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Liver Cirrhosis</term>
<term>Pyrazinamide</term>
</keywords>
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<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Chromatography, High Pressure Liquid</term>
<term>Female</term>
<term>Half-Life</term>
<term>Humans</term>
<term>Liver Function Tests</term>
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<front><div type="abstract" xml:lang="en">The pharmacokinetics of pyrazinamide (Pirilène) and its metabolites are evaluated in ten subjects with hepatic insufficiency, after an oral dose of 19.3 +/- 0.6 mg.kg-1 and the results are compared to those of a group of nine healthy subjects (control group). The results exhibit a marked reduction of the pyrazinamide total clearance (0.48 vs 0.84 ml.min-1.kg-1) and an increase in half-life from 9.19 h to 15.07 h in the patients group. The area under the curve of pyrazinoic acid (the main metabolite) is increased from 97 to 280 mg.h.l-1 with a half-life twice as much as that of the control group. The hepatic insufficiency entails a marked reduction of the common posology as well as a closer survey of the biologic hepatic parameters and of uric acid the renal elimination of which is inhibited by pyrazinoic acid.</div>
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<name sortKey="Lafont, O" sort="Lafont, O" uniqKey="Lafont O" first="O" last="Lafont">O. Lafont</name>
<name sortKey="Phan Hoang, T" sort="Phan Hoang, T" uniqKey="Phan Hoang T" first="T" last="Phan Hoang">T. Phan Hoang</name>
<name sortKey="Tranvouez, J L" sort="Tranvouez, J L" uniqKey="Tranvouez J" first="J L" last="Tranvouez">J L Tranvouez</name>
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<country name="France"><noRegion><name sortKey="Lacroix, C" sort="Lacroix, C" uniqKey="Lacroix C" first="C" last="Lacroix">C. Lacroix</name>
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