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PubMed1991

The disposition of antituberculous drugs in plasma of elderly patients. I. Isoniazid and hydrazine metabolite.

The plasma profiles of isoniazid (INH) and hydrazine (HYD) metabolite were compared in 18 elderly patients (67-89 years of age) and 19 young adult patients (19-59 years of age) on the first day and at one month after treatment for tuberculosis with INH, rifampicin (RIF) and pyrazinamide (PZA). There was no difference in the pharmacokinetics of INH between the two age groups. The clearance for INH at steady-state was significantly lower than after the first dose. After the first dose the maximum concentration (Cmax) for HYD was significantly higher (p less than 0.05) in the elderly (0.4 +/- 0.07 microgram/ml) than in the young (0.24 +/- 0.08 microgram/ml). HYD is produced in significant amounts during INH metabolism and this should not be neglected when evaluating INH related toxicity.

Acetylation↗
PubMed1990

[A therapeutic trial of a combination of 3 essential drugs in a short course of chemotherapy in tuberculosis. Results 6 months after the end of treatment].

250 patients suffering from pulmonary tuberculosis who were smear positive received a chemotherapy regime for 6 months combining Rifampicin and Isoniazid every day with a daily supplement of Pyrazinamide for the first 8 weeks. The three drugs given in the initial phase of treatment were administered either separately or in combined preparations according to the 2 controlled randomised groups. During the maintenance phase the drugs were given in a combined form in fixed proportions in the 2 groups. 6 months after the end of treatment the bacteriological results were similar in the 2 groups in the 144 cases which were analysed. Amongst 137 cases with bacilli which were initially sensitive to Isoniazid (68 cases with separate medicines at the beginning and 69 with combined drugs) there was no failure at 6 months, nor any relapse during the course of the first period of surveillance. Amongst 7 cases with bacilli which were originally resistant to Isoniazid (4 and 3 respectively), there were 2 failures at 6 months one in each group with acquired resistance to Rifampicin observed at the time of the failure. There was no difference in the therapeutic results observed whatever the presentation of drugs used during the initial phase of treatment.

Drug Combinations↗
PubMed1990

Effects of two pulmonary tuberculosis drug treatments and acetylator status on liver function in a Zimbabwean population.

In Zimbabwe patients with pulmonary tuberculosis who are acid-fast bacilli (AFB) negative in the sputum are treated in the two month intensive phase with isoniazid, thiacetazone pyrazinamide and streptomycin (regimen A). Sputum positive patients receive regimen A plus rifampicin (regimen B). Both groups continue treatment with isoniazid and thiacetazone. 21 patients on regimen A and 19 on regimen B had clinical assessment and liver function tests performed at weeks 0, 2, 4, 8, and 12 weeks of treatment (during and four weeks after, the intensive phase of 8 weeks). Acetylator status was also assessed, no significant difference was found between patients on regimen A or B (41 per cent and 45 per cent fast acetylators respectively). Liver function tests results (alanine aminotransferase and alkaline phosphatase) showed a persisting rise during the intensive phase on both regimens, and further rise after four weeks in the continuation phase, this further rise reaching statistical significance in regimen B. These results are unexpected when compared to other studies but the regimens under investigation are not used elsewhere. The significant rise after stopping intensive therapy in regimen B suggests some protective effect of rifampicin against the hepatotoxicity of the regimen, possibly the isoniazid/thiacetazone component. Acetylator status did not influence the degree of hepatotoxicity.

Alanine Transaminase↗
PubMedDate not supplied

[Effect of pyrazinoic acid on the transport function of the peritoneum--experimental studies].

Bidirectional transport of the urea, uric acid and albumin across parietal peritoneum was investigated in vitro under both normal conditions and following an administration of pyrazinoic acid. It was found that pyrazinoic acid decreased urea and uric acid transport from interstitial to mesothelial surface of the peritoneal membrane but did not affect the transport in reverse direction. Bidirectional transport of albumin remained unchanged. The obtained results are similar to those reported earlier and suggest that pyrazinamide actions are partially selective.

Albumins↗
PubMed1990

[Treatment of tuberculosis. Drug combinations, therapeutic problems and results in a 10-year case load].

The article describes the treatment of tuberculosis in 426 patients over a period of ten years. The length of treatment decreased during the period. The standard treatment was isoniazide and rifampicin, usually with initial administration of pyrazinamide. In pulmonary tuberculosis (n = 334) the median bacteriologic conversion time was five weeks. In 69 patients the medical regimen had to be changed because of side effects. Of the primary antituberculous drugs, isoniazide was the one producing the highest frequency of side effects. 31 patients showed lowered sensitivity to the usual antituberculous drugs and were treated with varying combinations of second line drugs. In two cases surgery was necessary in order to achieve bacteriologic conversion. Ten patients died of tuberculosis in spite of treatment. Five patients with pulmonary tuberculosis suffered a relapse after treatment. No relapse was noted among patients with extrapulmonary tuberculosis. There were large differences between the different pulmonary treatment centres in Eastern Norway as regards how they practised the Norwegian control routines.

Antitubercular Agents↗
PubMed1990

Mechanism of uricosuric action of AA-193 in DBA/2N mice.

Six strains of mice were investigated to find an animal model suitable for researching the mechanism of uricosuric agents. A clearance method and a pyrazinamide suppression test were used to examine the mechanism of urate excretion in the kidney and the mode of action of uricosurics, respectively. The negative correlation between the urinary urate excretion and the endogenous plasma urate level was observed, suggesting the net reabsorption of urate may vary between strains. DBA/2N mice showed the lowest fractional excretion of urate (0.278), and the effects of uricosurics on DBA/2N mice are analogous to those of humans. Our extensive study of the mechanism of urate excretion in DBA/2N mice has proven that the mouse strain is a useful model for the study of uricosurics. AA-193 (5-chloro-7,8-dihydro-3-phenylfuro[2,3-g]-1,2-benzisoxazole-7-carb oxylic acid) is a potent new uricosuric agent developed in our laboratory. In the present study, AA-193 was tested in DBA/2N mice and found to have a mode of action different from well-known uricosuric agents. It appeared to inhibit presecretory reabsorption in the proximal tubules.

Animals↗
PubMed1989

Intracranial tuberculomas. An assessment of a therapeutic 4-drug trial in 35 children.

35 children with suspected tuberculomas of the brain were given a therapeutic 4-drug trial of isoniazid, rifampicin, pyrazinamide and ethambutol. Their clinical and computed tomographic (CT) appearances were analysed retrospectively: 32 responded well to treatment with recognizable improvement on CT after 6 weeks. Three patients did not respond. One of these non-responders had a surgically removed temporal cystic astrocytoma. The majority presented with focal seizures and had a single hemispheral lesion. 14% had multiple lesions, 6% were in the cerebellum. Only 2 patients had raised intracranial pressure and required ventriculoperitoneal shunting.

Adolescent↗
PubMed1989

Change in the transport of uric acid under the influence of pyrazinoic acid: in vitro studies with human and rabbit peritoneum.

Bidirectional transport of uric acid (UA) through human and rabbit peritoneum, and its change under the influence of pyrazinoic acid (PA) was investigated in vitro. Fragments of parietal peritoneum were taken from the region of anterior abdominal wall from rabbits (the animal series) and from patients undergoing abdominal operations (the human series). Under control conditions, higher values of the UA transport were found in the rabbit peritoneum in comparison with the human peritoneum, but in both series it was maintained at a constant level throughout the experiment lasting 120 min. In rabbit as well as in human peritoneum it was found that PA depressed about 50% of the UA transport from the interstitial to the mesothelial side, leaving the opposite direction intact. The results obtained in vitro are in agreement with previous observations in a patient undergoing peritoneal dialysis that showed decreased peritoneal UA excretion evoked by pyrazinamide. The comparative analysis proves the rabbit peritoneum to be a good experimental model for further investigations of peritoneal urate transport in man.

Adult↗
PubMed1989

[A controlled survey comparing 2 short-term therapeutic regimes in lymph node tuberculosis].

To study the efficacy of short term chemotherapy in the treatment of peripheral glandular tuberculosis a controlled trial was carried out in Algiers in March 1982 comparing two therapeutic regimes. All the patients admitted to the study presented with glandular tuberculosis which was proved either histologically or bacteriologically. They were recruited in three clinics serving the Algerian population and were required to live in Algiers. The two anti-tuberculous regimes used consisted of an initial phase of four drugs: Rifampicin (R), Isoniazid (H), Streptomycin (S) and Pyrazinamide (Z) every day for two months. This initial phase was followed by R.H. every day for four months in regime A, making six months treatment in all and for seven months in regime B making nine months treatment in all. 141 patients were thus admitted to the study, of whom 117 could be used for analysis at the end of treatment. Of these 68 were female making up 58% of the total. 12 patients or 10% were under 15 years of age. After two years of review following the end of treatment there were nine therapeutic failures (7.7%) of whom five were in regime A and four were in regime B (no significant difference). Amongst the failures large volume nodes persisted in three patients and two patients presented with new nodes. The lymph nodes increased in volume at the end of treatment in two cases; and finally two patients presented again with fistulae at the end of treatment. There were eight unfavourable outcomes in nine patients under observation during treatment or at the end of chemotherapy. There was only one failure noted some time after the finish of treatment at the end of two years of follow up.

Adolescent↗
PubMed1989

[Which treatment for primary tuberculosis?].

Primary tuberculosis should be treated in all cases. In adults, the total treatment course for pulmonary tuberculosis can be shortened to 6 months. If the disease is not symptomatic, the rifampicin-isoniazid combination (10 mg/kg/day each) appears to be preferable to single drug therapy. In patients with symptomatic disease, pyrazinamide (30 mg/kg/day) should be added during the first 6-8 weeks and in some cases, corticosteroid therapy is also required. The drugs are usually well tolerated, but hepatic function should be monitored.

Acquired Immunodeficiency Syndrome↗
PubMed1989

[Effect of exercise on urate excretion].

Bidirectional renal urate transport was studied in normal male subjects, aged 21-26 yr. They performed a exhaustive running on treadmill for about 10 mins, after oral intake of each medicine. The used medicines were probenecid inhibited presecretory reabsorption, pyrazinamide inhibited tubular secretion and benzbromarone inhibited postsecretory reabsorption. The results were as follows: 1) Glomerular filtration rate decreased only 3 min after exercise, compared with resting level. 2) Presecretory reabsorption rate did not change substantially after exercise, compared with resting level. 3) Tubular secretion rate markedly decreased at 30 min and 1 hour after exercise, compared with resting level. 4) Postsecretory reabsorption rate changed as well as changes in tubular secretion rates.

Adult↗
PubMed1986

[Routine use of 6-month antitubercular treatment in 300 patients].

Over a 2-year period, all patients with incipient tuberculosis seen in a hospital unit were given a 6-month treatment consisting of rifampicine, isoniazide, pyrazinamide and ethambutol. A retrospective study of these 300 patients showed that the treatment was effective, with no failure if taken for more than 2 months. Relapses were rare when the drugs were taken regularly, the responsible M. tuberculosis strain was sensitive, and there was no associated malignancy (present in 1.4% of the cases). The drugs were moderately well tolerated, and treatment had to be modified because of side-effects in 4.6% of the patients. It also appeared that 57% of the patients fully complied with the prescription, and 16% were lost sight of by the hospital unit. Treatment was altered in 36% of the cases, but in 16% changes were introduced by private doctors for reasons which retrospectively proved to be without medical grounds. It is concluded that this 6-month chemotherapeutic regimen was effective in more than 98% of the cases, and that the main problem in management of tuberculosis is the patient's compliance with treatment.

Adolescent↗
PubMed1988

Renal handling of hypoxanthine and xanthine in normal subjects and in four cases of idiopathic renal hypouricemia.

Pyrazinamide (PZA) was used to study the renal handling of hypoxanthine, xanthine and uric acid in 2 normal subjects and in 4 patients with idiopathic renal hypouricemia; one patient was classified as having a postsecretory reabsorption defect, whereas the others were classified as having a presecretory reabsorption defect. In normal subjects, PZA suppressed strongly the excretion of xanthine as well as uric acid; however, it showed a weak effect on that of hypoxanthine. PZA suppressed all excretion of these 3 compounds in the patient with postsecretory reabsorption defect. PZA showed almost no effect on the excretion of either hypoxanthine, xanthine or uric acid in the patients with presecretory reabsorption defect.

Adult↗
PubMed1987

Hypouricemia due to subtotal defect in the urate transport.

Hypouricemia due to renal tubular defects is rarely reported. We report here our observations of two such patients who cannot be classified into any of the previously reported categories of renal hypouricemia. They showed no suppression of urate clearance to creatinine clearance ratio (Cua/Ccr) following the administration of pyrazinamide, and no increase of Cua/Ccr after probenecid. It is tempting to speculate upon the subtotal defect in the urate transport as a condition explaining the above results.

Adult↗
PubMed1986

Short-course tuberculosis chemotherapy studies conducted in Poland during the past decade.

During the past decade, six short-course (6-month) chemotherapy regimens were studied in which drugs were given daily and intermittently. Four regimens containing isoniazid, rifampin, and ethambutol caused little toxicity but yielded relapse rates (8-21%) which were unacceptably high. The safety of giving rifampin (450 or 600 mg) twice weekly was confirmed, however, and there was evidence that daily therapy during the 4-month continuation phase was no more effective than twice weekly isoniazid and rifampin. Once weekly therapy during the continuation phase was clearly inadequate. The use of four drugs (isoniazid, rifampin, pyrazinamide, and streptomycin) given daily during the initial 2 months of therapy followed by 4 months of twice weekly isoniazid and rifampin resulted in a nearly 100% cure rate. However, this regimen was not well tolerated by patients. Deleting streptomycin improved the tolerability of the regimen but appears to have slightly increased the frequency of treatment failure and relapse. A suggested model for choosing treatment regimens is presented.

Adolescent↗
PubMed1986

CNS tuberculosis.

Tuberculous meningitis is a rare, treatable neurologic disorder, in which early recognition is paramount because outcome depends greatly on the speed with which therapy is initiated. Patients with meningitis and CSF findings of low glucose, elevated protein and pleocytosis with evidence of tuberculosis elsewhere in the body (chest radiographs, positive tuberculin skin test), or a history of exposure to tuberculosis should be treated immediately with antituberculous medication. When the diagnosis remains uncertain, serial examination of the CSF for tuberculous organisms will often yield positive results. The CT scan may show hydrocephalus, a basilar arachnoiditis, or intraparenchymal lesions: tuberculomas. Hydrocephalus may respond to early shunting. Tuberculomas are best treated medically. Therapy should include INH and rifampin; ethambutol and pyrazinamide are suggested for the first 2 months of therapy. Steroids may be useful in diminishing the inflammatory response when altered consciousness or focal neurologic signs are present.

Biopsy↗
PubMed1986

[Daily ultrashort chemotherapy and intermittent short-term chemotherapy with 4 drugs of communicable pulmonary tuberculosis treated for the first time. Results of a cooperative multicenter study].

Three short-course regimens, all comprising isoniazide (H), rifampicine (R), streptomycine (S) and pyrazinamide (Z), are compared in a randomized prospective cooperative clinical trial. The drugs are given daily in a 3-month regimen (3-HRSZ), twice a week in a 6-month regimen (6-HRSZ2), and in a further two-phase 6-month regimen the 4 drugs are administered 3 times a week for the first 3 months followed by the administration of HSZ twice a week (without R) for further 3 months (3-HRSZ3/3-HSZ2). The number of patients admitted to study is 80, 144 and 139 respectively. The 3-month regimen has been stopped because of a high rate of relapses. 17 p.c. of the patients admitted have to be excluded from analysis for various reasons, out of these 5.8 p.c. because of adverse reactions. Two thirds of the patients had heavily positive sputum cultures at the start. 300 patients completed therapy. At the end of therapy cultures were negative in 94 p.c., 100 p.c. and 99 p.c. respectively. The rate of bacteriological relapses is 19 p.c. in 3-HRSZ, 9 p.c. in 3-HRSZ3/3-HSZ2 and 3 p.c. in 6-HRSZ2, during a follow-up period of 3-4 years after completing therapy. The acceptability was good in all treatment groups. Adverse reactions like "flu" were rarely observed. Increased blood urea was common but in general without clinical symptoms. Elevation of ALAT and ASAT was relatively frequent but mostly transient and without clinical importance. The results served as basis for the new "Recommendation for Treatment of Tuberculosis" and are interpreted with regard to practical consequences and possibilities for further rationalisation of treatment.

Adolescent↗
PubMed1987

Treatment of tuberculous meningitis: role of short-course chemotherapy.

Twenty-eight adult patients admitted consecutively with tuberculous meningitis were treated with pyrazinamide, isoniazid, rifampicin and streptomycin daily during the first two months, followed by isoniazid and rifampicin daily for seven months with intensive management of the complications during the active stage of the meningitis. Twenty-two patients completed the course of treatment and recovered with minimal morbidity in three patients. Two patients died in a vegetative state from other causes seven and nine months after the start of treatment. No evidence of recurrence of meningitis was observed in the 21 patients who were regularly observed for 12 to 29 months after completing treatment. Four patients dropped out during the early stage of treatment. Intensive chemotherapy of tuberculous meningitis with this regimen before the development of serious neurological damage can shorten the duration of treatment to nine months with a favourable outcome.

Adolescent↗