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C Guyonnaud

Publications and source records attributed to C Guyonnaud.

6 recordsLinked to original sources

Pharmacokinetics of pyrazinamide and its metabolites in healthy subjects.

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 less than or equal to 1 h) and showed a short distribution phase followed by an elimination phase of t1/2 beta = 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).

Chromatography, High Pressure Liquid↗

Haemodialysis of pyrazinamide in uraemic patients.

The pharmacokinetics of PZA during haemodialysis were determined in 6 patients with chronic renal impairment after a single oral dose of 25.7 (1.9) mg.kg-1. The dialysis clearance of PZA and of its metabolites were: pyrazinamide 132 ml.min-1; pyrazinoic acid 121 ml.min-1; 5-hydroxy-pyrazinamide 107 ml.min-1; 5-hydroxy-pyrazinoic acid 118 ml.min-1. The average amount extracted during a dialysis session of 4.1 h was 926 mg after an oral dose of 1700 mg. The high dialysability shows that PZA can properly be administered at the end of each dialysis session in the usual dose of 25 to 30 mg.kg-1.

Adult↗

Interaction between allopurinol and pyrazinamide.

Pyrazinamide (PZA) is increasingly used with isoniazid and rifampicin, in short-course antituberculous chemotherapy in service programme conditions. Complicating arthralgias occur due to hyperuricaemia induced by the inhibition of renal tubular secretion of uric acid by pyrazinoic acid, the main PZA metabolite. Allopurinol (Al), a hypouricaemic agent, provides no substantial clinical improvement. Pharmacokinetics of PZA and its metabolites were studied in six healthy volunteers, in a cross-over design, after a single oral dose of PZA alone and, in a second trial, after the same dose together with Al. Plasma and urinary concentrations were measured by high pressure liquid chromatography with a column of cation exchange resin. Analysis of the pharmacokinetic parameters showed that Al induced marked changes in levels of PZA metabolites and accumulation of pyrazinoic acid. Despite decreasing uric acid synthesis, allopurinol increased plasma concentrations of pyrazinoic acid, which is directly responsible for the inhibition of renal urate secretion. Other drugs, which do not involve xanthine oxidase inhibition, should be used in the treatment of this side effect of chemotherapy.

Adult↗

[Microdetermination of pyrazinamide and its metabolites (pyrazinoic acid, 5-hydroxypyrazinoic acid, 5-hydroxypyrazinamide and pyrazinuric acid) in plasma and urine with liquid chromatography].

The method reported here for determining pyrazinamide and its metabolites (2-pyrazinoic acid, 5-hydroxypyrazinamide, 5-hydroxypyrazinoic acid and pyrazinuric acid) consists of diluting urine or acid deproteinisation of serum followed by chromatography on a cation-exchange column. The column length and the detection system (ultraviolet or fluorimetry) allow for a very good separation of the different compounds; the sensitivity of the method makes it suitable for pharmacokinetic studies.

Chromatography, High Pressure Liquid↗

[Elements to be taken into consideration in the establishment and supervision of respiratory rehabilitation programs].

For a good respiratory re-education, the handicap must be analyzed together with its causes and mechanisms, in relation with the patient's social environment, his age and profession. The handicapping factors should be analyzed in a medico-social (pollution, weather) and medical context by detecting the affection involved and the functional analysis. The latter is deduced from the clinical signs and measurements defining the functional syndrome justifying an appropriate treatment. The importance of the handicap is drawn out of the clinical measures of maximum effort studied by ergometry. There are 2 levels of handicap (without alteration of blood gases at rest) and of respiratory insufficiency: simple or complicated by decompensation bouts enabling the choice of re-adapatation methods correlated with age an environment. Clinical and functional supervision as well as the study of the integration in the environment, form the basis of the analysis of results obtained in 2 comparable groups or in one homogeneous group subjected first to a simple medical treatment, then to re-adaptation.

Humans↗