Biomedical subjects
Publications and source records attributed to H Duwoos.
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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.
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).
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.
Numerous studies have shown that longterm oxygen therapy in hypoxaemic patients with chronic airflow obstruction (BPCO) is capable of improving the prognosis and decreasing the risk of cardio-respiratory decompensation; in addition sometimes physical capacity and intellectual capacity is improved. Another result often noted is a reduction in the mean hospital stay which corresponds to an improvement in the quality of life. A PaO2 constantly below 55 mmHg (7.3 kPa) is defined by the majority of authors as a precarious state. At this level even a small change in alveolar ventilation or disturbance of distribution would lead to an important fall in the oxygen content of the arterial blood. The stability of the PaO2 during the weeks of respiratory reeducation with specially controlled medical treatment, as well as the willing consent of the patient and his family, are indispensable conditions for the prescription of OLT. When hypoxaemia is of moderate severity (PaO2 between 50 and 60 mmHg (6.6-8 kPa), prolonged medical treatment (with abstention from tobacco) for at least two months is advised and a study of complementary criteria to further validate the indications for oxygen. Such features would include a worsening of the hypoxaemia during exercise of 30 to 40 watts (PaO2 less than 50 mmHg, 6.6 kPa), an elevated haematocrit (greater than 55%), a rise of the P (A-a)O2 (greater than 30 mmHg or 4 kPa), a nocturnal desaturation even in the absence of apnoea (oxyhaemoglobin saturation (SaO2) of less than 80% for more than 50% of the time asleep). Added to these criteria are the radiological, echographic and clinical signs of the effect of hypoxaemia on the pulmonary circulation. Frank pulmonary arterial hypertension observed in hypoxaemia of moderate severity when the PaO2 is in the region of 55 mmHg and is an argument for the prescription of OLT. Amongst the developing criteria, exacerbations of respiratory encephalopathy, intellectual deterioration, progressive wasting, permanent ventilatory embarrassment with tachypnoea, should be borne in mind as the occasion arises. A schedule of 18 hours per day (without stopping for more than 3 hours) is necessary to obtain an improved survival and places a great demand on patient co-operation and on their environment. A prolonged educational programme is required. To achieve such a schedule the use of portable oxygen may be justified so that patients can lead a normal social life.(ABSTRACT TRUNCATED AT 400 WORDS)
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.
One hundred seventeen patients with severe chronic obstructive pulmonary disease whose PaO2 in a stable clinical state ranged from 41 to 59 mmHg, were included in a multicentric controlled study on the effects of long-term O2 therapy (LTO), and the results of the 3-month probationary period are given here. Arterial blood gases were checked every month in order to assess the stability of hypoxemia. Time 0 represented the beginning and T3 the end of the probationary period. Patients whose PaO2 at T3 was still between 41 and 59 mmHg could be accepted for the long-term study (Group A), whereas patients whose PaO2 had increased over 59 mmHg were excluded (Group B). Only 77 patients could be followed up regularly from T0 to T3 (40 patients were lost to follow-up, missed some visits, or suffered from acute exacerbations of the disease) and 23 of them had a PaO2 at T3 that exceeded 59 mmHg (Group B), allowing the inclusion of 54 patients (Group A) in the long-term study. Patients in Groups A and B did not differ with regard to pulmonary volumes, PaCO2 at T0 or a past history of right heart failure. Arterial O2 tension at T0 was slightly and significantly (p less than 0.02) lower in Group A (51.3 +/- 5.5 mmHg) than in Group B (54.5 +/- 3.8 mmHg), but there was an important overlapping of individual results from one group to another.(ABSTRACT TRUNCATED AT 250 WORDS)
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Having given a definition of chronic pulmonary patients and of readaptation by reference to the W.H.O. and to the results of an international survey and the study group of the special Unit of the European Society of respiratory Physiopathology, the authors report a critical study of the conception and the present aims of readaptation. They successively present the therapeutical, medico-social and psychological aspects of readaptation, the different techniques used today, and summarize the present functioning of Europeans centres of readaptation. Finally they draw the main lines of a program of readaptation with the public health scheme and envisage the problems of organization and functioning.
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.
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