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Biomedical subjects

L Balant

Publications and source records attributed to L Balant.

At least 37 records · Page 2Linked to original sources
PubMed1986

[Depressive states in the elderly and their treatment].

The clinical classification of depressive states has undergone considerable modification in the past few years. More particularly, the various clinical forms described earlier in relation to age or dubious etiological hypotheses have been reorganized within the framework of general categories of depression established according to clinical criteria. This development has been largely due to the work accomplished by the American Psychiatric Association Task Force and its Diagnostic and Statistical Manual of Mental Disorders, which has become a standard reference work worldwide. With its precise criteria, this classification enables clinicians to adjust therapeutic indications more readily to each particular case. Monotherapy is the rule of thumb for the pharmacological treatment of depression, particularly in the elderly. Combination of medications in the treatment of agitated or melancholic depressive states must be limited to situations in which it is absolutely necessary, and in such cases it is even more important to monitor blood levels than in monotherapy. When there is a significant psychotic component to major depression (hallucinations, delusions), it is advisable to undertake specific antipsychotic treatment before initiating antidepressant medication. In the majority of cases it is possible to treat depressive states in the elderly by appropriate selection of both medication and dosage, and by careful clinical attention to the patients' physical and psychological well-being.

Aged↗
PubMed1985

Effect of oxidative polymorphism (debrisoquine/sparteine type) on hepatic first-pass metabolism of bufuralol.

Bufuralol is a beta-adrenoceptor blocking drug whose oxidative metabolism is under the same genetic control as debrisoquine and sparteine. The pharmacokinetics of bufuralol were studied in 10 healthy subjects (7 extensive and 3 poor metabolizers of debrisoquine) after oral and intravenous administration. In extensive metabolizers the systemic availability of bufuralol was 43%. Poor metabolizers were characterized by a considerable increase in systemic availability due to a corresponding decrease in hepatic first-pass metabolism. After oral administration of bufuralol non-linear kinetics may occur.

Adrenergic beta-Antagonists↗
PubMed1984

Plasma haloperidol levels and therapeutic response in acute mania and schizophrenia.

In an open study, 18 patients suffering from an acute episode of schizophrenia and 18 patients with severe mania were given haloperidol at different dosage levels. Haloperidol plasma concentrations were measured and the status of the patients was evaluated at intervals using the Brief Psychiatric Rating Scale (BPRS). No correlation was found between the oral dose and the plasma concentrations in the schizophrenic group, but there was a low correlation for manic patients. In both groups, however, there was a correlation between these two parameters when the drug was given intramuscularly. There was no correlation between haloperidol plasma concentrations and the BPRS scores. Of the 36 patients 28 responded well to the treatment and were discharged from hospital. A good relationship between the clinical status as observed by the clinicians and the BPRS score was found. Plasma haloperidol concentration measurement was found to be a useful tool for the detection of non-compliance or excessive plasma levels. Accordingly, the present study indicates the value of drug level monitoring as a means to improve therapy.

Administration, Oral↗
PubMed1983

[Quantitative approach to drug compliance of diabetics].

Many patients do not take their medication according to the instructions of their physician. Patient compliance is particularly poor in the long-term treatment of diseases, which produce only minor symptoms in the patient. The aim of the present study was to quantitate patient compliance in diabetics treated with tolbutamide. The amount of tolbutamide taken by the patient was estimated on the basis of its 24 hours urinary excretion. The collection of the 24 hours urine is a standard procedure in our outpatient clinic for the measurement of glycosuria. The study involved 33 diabetics followed over several months. In those reliable patients, who conscientiously took their medication, we found a good correlation between the prescribed dose and the 24 hours urinary excretion. In contrast, when the data from the entire group of 33 out-patients was evaluated, the correlation between these two parameters of prescribed dose and urinary excretion was poor. The correlation between urinary excretion and the dose admitted by the patient was just as poor. According to our results, only one out of two diabetics took the prescribed dose. After our initial observations, we informed the outpatients about their inclusion in this study. In spite of the fact that the patients knew that they were under observation for compliance, we found large interindividual differences in the urinary excretion of tolbutamide over several months. In contrast, the intraindividual variability was low. We found that interviews with patients are a poor means to detect non-compliance, whereas urinary excretion measurements appear to be more reliable.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus↗
PubMed1983

[Pharmacokinetic and clinical consequences of the genetic polymorphism of oxidation].

Bufuralol is a beta-adrenoceptor blocking drug whose metabolism is under the same genetic control as debrisoquine. Bufuralol appears to be a sensitive tool for characterization of this pharmacogenetic variation. After test drug absorption, one single blood collection allows separation between extensive and poor metabolizers. In Switzerland, the poor metabolizer status has a prevalence of 8%. In poor metabolizers bufuralol plasma concentrations are very high, an observation of interest when considering the occurrence of side effects of the drug. In addition to disease-induced variability in drug response, oxidation polymorphism is a major source of interindividual variations in drug effect. As the metabolism of numerous drugs is affected by this pharmacogenetic variation, the question arises whether systematic screening should not be considered.

Adrenergic beta-Antagonists↗
PubMed1983

Contribution of the genetic status of oxidative metabolism to variability in the plasma concentrations of beta-adrenoceptor blocking agents.

The oxidative metabolism of bufuralol is under the same genetic control as that of debrisoquine and sparteine. 154 fasting volunteers received a 30 mg tablet of bufuralol and a blood sample was taken 3 h later. In poor metabolizers (8% of the sample) the plasma bufuralol concentrations were very high and the metabolite concentrations were low. The genetic oxidative status is a major source of interindividual variation in the plasma concentration of drugs that undergo oxidative metabolism.

Adrenergic beta-Antagonists↗
PubMed1983

Salivary electrolytes and digitalis.

The hypothesis that an increase in salivary concentration of certain electrolytes (Ca X K) is a sign of digitalis intoxication was tested in 16 untreated health volunteers, 29 digitalized heart failure patients and four further healthy volunteers given digoxin. Salivary electrolyte levels were raised in only about half the digitalized patients and blood levels of digoxin were not always higher in these patients than in those with normal electrolyte concentrations. The salivary electrolyte levels of the healthy volunteers given digoxin remained normal. These findings would seem to rule out the possibility that digitalis is responsible for the changes in salivary electrolytes observed in certain cases of heart failure. A very marked correlation (P less than 0.00002 by Fisher's exact probability test) was found, however, between an increase in the product of salivary calcium and potassium (Casal X Ksal) and the presence of clinical signs of poorly compensated heart failure. It is suggested that this might be a result of adrenergic stimulation, which is known to occur in heart failure, affecting the salivary glands.

Adult↗
PubMed1983

The genetic control of drug oxidation in the liver.

Hepatic drug oxidation is a major source of interindividual variations in drug behaviour. A wide spread of the pharmacokinetic parameters of extensively oxidized drugs is a common observation. For such compounds, in the absence of polymodal distribution of the kinetic parameters, no distinct genetic influence can be detected. The discovery that the urinary excretion of debrisoquine and its main hydroxylated metabolite displays a bimodal pattern opened a new field in the study of hepatic metabolism. This new genetic polymorphism now concerns the oxidative metabolism of numerous substances such as antihypertensive agents, antidepressants, antiarrhythmic drugs and various other unrelated compounds. The poor metabolizer phenotype is observed in some 8% of individuals in European populations. We have shown that the oxidative metabolism of beta-adrenoceptor blocking drugs is under the same genetic control as debrisoquine. Using bufuralol as a test drug, we have studied the influence of polymorphic oxidation on interindividual variations of parent drug and metabolite plasma concentrations. It appears clearly that oxidation polymorphism is a major factor of variability in hepatic drug handling. This fact has important clinical and pharmaceutical implications.

Adrenergic beta-Antagonists↗
PubMed1982

[Pharmacokinetic study of a cephalosporin: cefoperazone in patients with a Kehr drain].

Cefoperazone is a semi-synthetic cefalosporine for parenteral use which has an excellent activity against a wide range of grampositive and gramnegative bacteria, especially Pseudomonas aeruginosa, Enterobacter, Proteus indole positive and Serratia marcescens. The pharmacokinetics of the new antibiotic have been studied in patients who had undergone cholecystectomy and choledochotomy for lithiasis and who required T-tube drainage of the bile duct. Five patients were anicteric and one was icteric. Mean serum concentration of cefoperazone determined by a microbiological method) measured after a two-hour intravenous perfusion of 2 g cefoperazone was 198.6 microgram/lm; this level is higher than the mean level measured in normal subjects (134 microgram/ml) but lower than the mean level measured in patients with hepatic insufficiency (208 microgram/ml). Apparent half life of elimination was longer (mean 4.1 hours) in the patients than in controls (mean 1.6 hours) and compares with that of patients with hepatic insufficiency (mean 4.3 hours). The distribution volume and renal clearance are similar to that in healthy volunteers and patients with hepatic insufficiency. Extrarenal clearance of cefoperazone was significantly lower in our patients (15.8 ml/min), as it is in patients with hepatic insufficiency (7.3 ml/min), than in the control group (59.4) ml/min). Cefoperazone concentrations in the bile were 10-20 times higher than those in the serum; in the icteric patient the concentrations achieved were still higher than the MIC values for organisms commonly encountered in the bile. These results open the way to the use of cefoperazone to treat infectious biliary diseases, particularly angiocholitis, which need a high biliary antibiotic concentration.

Adult↗
PubMed1982

Role of oxidation polymorphism on blood and urine concentrations of amitriptyline and its metabolites in man.

We have measured the metabolites (demethylated and hydroxylated) of amitriptyline in a group of seven normal volunteers. They were phenotyped as extensive or poor metabolizers using debrisoquine and bufuralol. The results demonstrate that the oxidative metabolism (aliphatic hydroxylation) of amitriptyline is under the same genetic control as that of debrisoquine and bufuralol. However, phenotypic polymorphism cannot be used to predict amitriptyline blood concentration after a single oral dose, since the principal metabolic pathway of amitriptyline is demethylation and not aliphatic hydroxylation.

Adult↗
PubMed1981

[Retention of metabolites of a beta-blocking drug, oxprenolol, in renal insufficiency].

The pharmacokinetics in blood of oxprenolol and its glucuro-conjugated metabolites has been investigated in healthy volunteers and hemodialyzed patients; in addition, the effect of the drug on the heart rate has been measured. Renal insufficiency does not modify the elimination kinetics of oxprenolol, but it does lead to massive retention of the glucuro-conjugated derivatives on multiple dosing. The present study failed to show hydrolysis of the conjugates with liberation of the active parent compound. In addition, from measurement of the exercise-stimulated heart rate it can be concluded that active metabolites of oxprenolol are absent. The duration and intensity of the effect of a single dose of the drug were comparable in the healthy volunteers and the patients with renal insufficiency.

Biotransformation↗
PubMed1981

[Pharmacokinetic study of a cephalosporin, cefoperazone, in liver failure].

The pharmacokinetics of cefoperazone, a semi-synthetic cephalosporin for parenteral use with a spectrum covering P. aeruginosa, E. cloacae, indole-positive Proteus and S. Marcescens, was studied after a 2-h intravenous infusion of 2 g of the drug in 6 patients with moderate liver function impairment (viral hepatitis in 4 cases, alcoholic fatty liver and cirrhosis in 2 cases). At the end of the infusion, mean serum concentrations (determined by a bioassay) were 208 microgram/ml in the patients and 134 microgram/ml in healthy volunteers. The half-life was 4.3 h in patients and 1.6 h in healthy volunteers. Volume of distribution and renal clearance were similar in the two groups. Extrarenal clearance of cefoperazone was lower in the patients (7.3 ml/min) than in the control group (59.4 mg/min). Urinary excretion of biologically active drug was markedly increased in the patients (79% of the dose) compared with healthy volunteers (24%). This study provides evidence that liver function impairment increases with both the apparent half-life of elimination and the urinary excretion of the drug. The results raise the question of the desirability of cefoperazone dosage adjustment in patients with hepatic diseases.

Adult↗
PubMed1981

[Diagnosis of lactase deficiency with the expired hydrogen (H2) test].

To determine the sensitivity and specificity of breath hydrogen (H2) in detecting lactase deficiency, breath H2 collected by end-expiratory sampling and capillary blood glucose were measured after ingestion of 50 g of lactose in 36 patients with biopsy-proved isolated lactase deficiency, 42 with normal lactase activity and 6 with lactase deficiency secondary to mucosal lesions. All patients had digestive symptoms clinically compatible with lactose malabsorption. The maximum increase in breath H2 concentration was more than 1.1 mumol/l (25 ppm) in all patients with isolated lactase deficiency, and less than 0.88 mumol/l (20 ppm) in 88% of patients with normal lactase activity; there were 5 false-positive results, attributed in one case to small bowel colonization and in another case to rapid transit after gastric surgery. Secondary lactase deficiency was accurately detected by neither breath H2 nor blood glucose.

Adult↗