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L Balant

Publications and source records attributed to L Balant.

At least 37 records · Page 2Linked to original sources
PubMed1978

[The exhaled hydrogen test: its value in the quantitative diagnosis of carbohydrate malabsorption].

A study has been conducted to determine the accuracy of breath-H2 measurements for quantitating the malabsorption of small amounts of carbohydrate. H2 pulmonary excretion was measured after an overnight fast at 30-min intervals for 4 h in 7 healthy subjects after ingestion of 4 doses of lactulose (2.5,5,10 and 50 g). In 3 subjects the test was repeated without lactulose. The volume of H2 excreted was directly proportional to the amount of ingested lactulose: mean cumulative H2 excretion over a 2-h period after 5, 10 and 50 g was 2.9, 6.6 and 37.6 ml H2 respectively; H2 response after the 2.5-g dose was not perceptible. Individual H2 excretion before lactulose ingestion was highly variable: 0.096 +/- 0.075 mlH2 (mean +/- 1 SD); the individual base line rate over a fasting period showed marked fluctuations. It is concluded that the inter- and intraindividual variations of H2 excretion limit the accuracy of the H2 breath test for quantitating malabsorption of small amounts of carbohydrate.

Breath Tests↗
PubMed1978

[Role of metabolites in the relationship between pharmacokinetics and the effect of beta blockers. Studies on tolamolol and bufuralol].

Plasma concentrations of tolamolol and bufuralol (beta-blocking agents) were measured after oral and intravenous administration to healthy volunteers. The plasma levels of their main metabolite was also determined. Simultaneously, the effect of the drugs on the heart rate and blood pressure was monitored under various stimuli (isoproterenol, exercise or orthostatism) and Valsalva maneuver. When given orally, the two drugs are extensively metabolized by a hepatic first-pass effect. After reaching the systemic circulation, they are metabolized in the liver to hydroxylated derivatives with similar pharmacologic activity as the parent molecule. For tolamolol it is possible to demonstrate a good correlation between parent drug blood levels and the pharmacodynamic effect; this relation is less evident for bufuralol. The pharmacokinetic analysis of the behaviour of the two beta-blocking agents and their main metabolite makes it possible to explain this difference in part. The results of the present study emphasize the importance of measuring metabolites when dose-action relationships are investigated.

Administration, Oral↗
PubMed1978

[D-xylose absorption test. A pharmacokinetic and statistical study].

D-xylose pharmacokinetics has been studied in 6 healthy subjects by serial measurement of blood and urinary levels following oral and intravenous administration of two doses of D-xylose (5 and 25 g successively). Furthermore, patients with obesity, renal or hepatic insufficiency, or with a T-drain after cholecystectomy, are also investigated. Both the rate and completeness of D-xylose absorption and the apparent distribution volume of D-xylose present noteworthy interindividual variations, so that the time and value of the peak blood level are highly variable as between healthy subjects. Renal insufficiency increases the apparent elimination half-life of D-xylose and notably reduces D-xylose renal excretion. This study provides pharmacokinetic evidence of the very wide range of blood and urinary levels observed in the D-xylose tolerance test, and emphasizes the fact that D-xylose urinary excretion alone is not a reliable index of intestinal absorption.

Administration, Oral↗
PubMed1978

[Proteinuria].

Explore the source record for details and available documents.

Child↗
PubMed1977

[Hypoglycemic sulfonylurea metabolites: clinical interest. Experiences with glibenclamide in the rat].

Glibenclamide, a hypoglycemic sulfonylurea, is extensively metabolized by the body and eliminated primarily in the form of its hydroxylated derivatives. The major metabolite, 4-trans-hydroxy-glibenclamide, is usually cleared rapidly from the bloodstream, but in certain pathological states (e.g. renal failure) blood levels of this product may increase. A protocol therefore was designed to test the hypoglycemic potency of this important metabolite in rats. Various quantities were injected intraperitoneally, and alterations in blood glucose concentrations were measured during a 5-hour period and compared to those in animals similarly treated with glibenclamide and in saline-injected controls. Using the dose capable of decreasing blood glucose levels by 30% (ED30) as a comparative index, it was observed that the metabolic has a marked hypoglycemic activity; though 6--7 times less potent than the parent drug, 4-trans-hydroxy-glibenclamide is nevertheless more potent than tolbutamide. Thus, while the glibenclamide metabolite probably has little influence on blood glucose when its clearance is normal, this product may exert marked effects if allowed to accumulate in the blood, as for example in renal failure. Finally, the role of such sulfonylurea metabolites should be taken into account when attempting to explain the occasional excessive and sustained hypoglycemia which occurs in some diabetic patients treated with these drugs.

Animals↗
PubMed1977

[Side effects of nalidixic acid in a patient with severe renal failure. Clinical study and proposal of a pharmacokinetic model].

Side effects due to ingestion of nalidixic acid in a 46 year old patient with phenacetine-induced interstitial nephritis and severe renal failure are reported. This observation underlines the point that, besides the direct neurotoxic effect of nalidixic acid, disturbance of the acid-basic equilibrium could be seen in patients with renal failure in particular. A hypothetical pharmacokinetic model suggests that two metabolites of nalidixic acid could provide enough hydrogen ion to induce acidosis in cases of renal failure.

Acid-Base Imbalance↗
PubMed1977

Behaviour of glibenclamide on repeated administration to diabetic patients.

Six maturity onset diabetic patients took glibenclamide 5 mg by mouth, every morning 10 min before a standard breakfast. Serum levels of immunoreactive glibenclamide, glucose and immunoreactive insulin were measured repeatedly on the first and 15th days of treatment. Measured glibenclamide blood levels were in close agreement with an analogue computer simulation of data obtained from healthy volunteers: there was no accumulation of drug in the blood, but there was strong evidence for the existence of a slowly equilibrating "deep" compartment. Considerable insulin release and correction of the breakfast-induced hyperglycaemia were observed immediately after administration of the drug, as well as 5 h later, at lunch time. The clinical significance of blood levels of glibenclamide, as well as the correlation of pharmacokinetics with pharmacodynamics, are discussed in the light of these results.

Administration, Oral↗
PubMed1976

[Electrocardiograms of digitalis intoxication. Reevaluation].

Serum digoxin concentration and ECG were recorded 111 times in 96 patients taking digoxin. The generally accepted ECG criteria of digoxin concentration seem greatly to overestimate the incidence of toxic cases. According to these criteria 63 ECGs in this study would have been regarded as toxic, whereas toxicity (defined by the association of serum digoxin elevation and clinical symptoms of toxicity) was actually present in only 11 cases.

Adult↗
PubMed1976

[Pharmacokinetics of two beta blocking drugs: detection of a pharmacogenetic abnormality].

10 healthy male volunteers received orally either 100 mg tolamolol or 20 mg bufuralol. These experiments were repeated by intravenous administration of 10 and 5 mg respectively of these two drugs. Plasma levels of the parent drugs and their main metabolite were measured. In one subject, the apparent half-life of elimination was increased from 2.5 h (normal subjects) to 5 h for both drugs. This prolongation of the half-life is associated with low plasma levels of the metabolites, a peculiarity which can be explanined by a decreased rate of metabolism for these two drugs. This anomaly may explain the marked orthostatic hypotension observed only in this subject. The likelihood of a pharmacogenetic defect is discussed.

Administration, Oral↗
PubMed1976

[Clinical pharmacokinetics].

The action of a drug depends on the quantity which reaches the site of its pharmacological action and how long it remains there. The necessary vital processes of the body dilute the active principle into different compartments of distribution, transform it into metabolites, and excrete it. Since a time duration of drug presence at the site of action is vital for the cure of disease, a comprehensive and quantitative expression of these time courses of drug distribution as a function of dose and route of administration is necessary for the establishment of proper dosage regimens for the treatment of disease and the avoidance of toxicities. The purpose of pharmacokinetics is to study these phenomena and to construct models suitable to explain them and to predict the behavior of drugs in conditions not yet studied. In this review some basic principles of pharmacokinetics (i.e. the compartment, the volume of distribution, the elimination half-life, etc.) are explained. Their clinical implications are shown in the case of multiple dose administration and in the study of the relations existing between blood levels of digoxin and the pharmacological action of this drug.

Body Weight↗
PubMed1976

Renal failure, drug pharmacokinetics and drug action.

Patients with renal insufficiency often react abnormally to a number of drugs. Small doses that are safe under normal conditions may cause severe and even fatal side-effects. As a consequence, modification of the usual drug dosage of these drugs in required in renal insufficiency. Since the risk of retention concerns only those drugs which are mainly excreted by the kidney, it is possible to establish a mathematical relationship between glomerular filtration rate and the rate of drug elimination. These relationships serve as a basis for the determination of the proper dosage regimen for the individual patient. Such dosage adaptation for intermitten drug administration can be obtained by two methods and a series of compromises between them: (1) increase of the dosage interval without changing the dose, and (2) reduction of the does without changing the frequency of administration. One must however, not only consider inadequate drug elimination but also a number of other factors. Some of these modify the behaviour of the drug, such as hypoalbumineamia, which causes an increase of the unbound portion of the drug; anomalies of the volume of distribution, as found in patients with oedema; metabolic disturbance; alteration of absorption from the gastro-intestinal tract, etc. Other factors are related only indirectly to the pharmacokinetic behaviour of the drug. Frequently, there is an increased sensitivity to the undesirable side-effects of certain drugs in patients with renal insufficiency, causing the level of tolerance to be lowered compared with normal patients. Such an effect probably involves functional or morphological modifications of the drug receptors, or interaction with substance retained in renal insufficiency. Furthermore, drugs may accentuate the consequences of the nephropathy or have increased nephrotoxicity for those with diseased kidneys. It is with these important reservations that a critical analysis of the proposed methods of adapting drug dosage in renal insufficiency is presented. An appendix tabulates the effects of renal insufficiency on the behaviour of 117 drugs. Irrespective of the method used to calculate drug dosage, all patients with renal disease must be monitored closely, particularly for signs of unexpected drug toxicity.

Drug Administration Schedule↗