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Biomedical subjects

L Balant

Publications and source records attributed to L Balant.

At least 55 records · Page 3Linked to original sources
PubMed1981

Simultaneous tubular excretion and reabsorption of pindolol in man.

The plasma concentrations of pindolol have been examined following the administration of single doses of 15 mg tablets to eight healthy male subjects. The apparent half-life of elimination in plasma (t1/2 = 4.05 h) and in urine (t1/2 = 3.21 h) was calculated using conventional pharmacokinetic methods. The renal clearance was estimated by plotting urinary excretion rates versus plasma concentrations; for all subjects these plots were curved. In addition to these graphical estimations, the plasma concentrations of pindolol and the urinary excretion data for each volunteer were simultaneously fitted using a one or two-compartment open body model; a computer program using non-linear regression algorithms was used. This procedure did not give an adequate fit to the data. Another type of data analysis, using a population - based model, permitted us to show that the renal elimination of pindolol in man comprises of two separate processes - tubular secretion and reabsorption, which was partially saturable under the experimental conditions. The theoretical relevance and clinical significance of these findings are discussed.

Absorption↗
PubMed1980

[Initial aspects of the changes in diabetic proteinuria].

Proteinuria was analysed quantitatively and qualitatively in 156 diabetics and 63 matched controls. The study was limited to patients with a proteinuria of less than 100 ng/min in the recumbency. The urinary proteins were analysed using cellulose acetate electrophoresis, immunoelectrophoresis and sodium dodecylsulfate poly-acrylamide gel electrophoresis. Abnormal urinary protein patterns were more frequent in diabetics than in the controls (p less than 0.01). However, when the subjects were divided into 2 groups according to their age, the limit being arbitrarily chosen at 60 years, the differences were statistically not significant in the older group. By contrast, in the younger group, the proportion of perfectly normal patterns was significantly decreased in diabetics as compared to the controls (p less than 0.005). In our diabetic population, chosen on the basis of a quantitatively normal proteinuria, no clear relation could be found between the abnormalities of the urinary protein electrophoretic patterns and the patient's clinical data, with the exception of vascular and cardiac complications. Our results suggest that qualitative changes of urinary proteins might be the first signs of renal complications in diabetic patients and that diabetes might constitute an additional cause of aging for the kidneys.

Adult↗
PubMed1980

[Kinetics of cefoperazone and cefoperazone and cephalothin in rat tissues].

In order to study the behavior of two cephalosporines in various tissues, 100 mg/kg of cefoperazone (CPZ) or cefalotine (CLT) were administered intraperitoneally to Wistar rats. The animals were sacrificed by groups of 6 at intervals ranging from 30 min to 6 hours after the injection and bioassay of the antibiotic was carried out in 9 organs, the serum, and urine. There are marked differences in tissue affinity for each antibiotic, as well as between the tow antibiotics. With the exception of the renal medulla, CPZ penetrates most tissues better than CLT. This difference is particularly striking in the liver. The decline of concentrations is nearly the same in tissues and serum; it is 2--3 times slower for CPZ. Concentration of CPZ exceed 1 microgram/g for more than 6 hours in the kidney and 4 hours in the liver, whereas CLT cannot be quantified after 2 hours in the kidney and after 1 hour in the liver. As has been noted for other antibiotics, plasma protein binding has only limited influence on cephalosporin penetration into tissues. This study of pharmacokinetics in tissues shows that CPZ permeates well those tissues where it is supposed to be effective and remains there longer than CLT. The study illustrates a method which provides a better understanding of the mechanisms responsible for antibiotic action.

Animals↗
PubMed1980

Influence of renal failure on the hepatic clearance of bufuralol in man.

The beta-blocking agent bufuralol is subject to first-pass metabolism and is eliminated from the body almost entirely by biotransformation. Its major metabolite in plasma (1'-hydroxy-bufuralol) is biologically active and may contribute to the pharmacological effect of the drug. The effect of renal failure on the behavior of the parent compound and three of its metabolites was studied by comparing their kinetics in normal volunteers and in patients with severe renal insufficiency. Bufuralol was given orally to all subjects (20 mg); some of the healthy volunteers also received the drug intravenously (5 mg). Renal failure was found to be associated with a marked increase of the areas under the plasma concentration-time curves of the parent compound, whereas its halflife of elimination was not markedly influenced. The behavior of 1'-hydroxy-bufuralol was consistent with a decreased renal clearance. The behavior of bufuralol in patients with renal failure was analyzed using the clearance approach. From this analysis it appears that the presystemic biotransformation of bufuralol is decreased in renal failure and that changes in systemic clearance are compensated in our patients by modifications of the volume of distribution, resulting in little net change in the halflife of elimination.

Adrenergic beta-Antagonists↗
PubMed1980

[Clearance concept applied to pharmacokinetics: 1. Application for the study of tolamolol (beta-blocking agent) in healthy volunteers (author's transl)].

Pharmacokinetics is often performed using models derived from the properties of exponential equations in order to analyse the behaviour of drugs in normal and pathological situations. A new approach based on the clearance concept allows an interpretation of the experimental data with models incorporating some physiological parameters, such as hepatic blood flow. The present study shows how the clearance concept may be used for the treatment of the results obtained in healthy volunteers. In particular, it allows an estimation of the importance of hepatic first-pass metabolism and validates the model used for the analyses of the kinetics of tolamolol.

Humans↗
PubMed1980

[Clearance concept applied to pharmacokinetics: 2. Experience with tolamolol (beta-blocking agent) in renal insufficiency (author's transl)].

Tolamolol is subject to first-pass metabolism and is eliminated from the body almost entirely by biotransformation. Its major metabolite in plasma (4-hydroxy-tolamolol) is biologically active and may contribute to the pharmacological effect of the drug. The effect of renal failure on the behaviour of the parent compound and of its metabolite was studied by comparing their kinetics in normal volunteers and in patients with severe renal insufficiency. Tolamolol was given orally to all subjects at a 100 mg dose. Renal failure was found to be associated with a marked increase of the areas under the plasma concentration-time curves of the parent compound, whereas its half-life of elimination was not markedly influenced. The behaviour of tolamolol in patients with renal failure was analysed using the clearance approach. From this analysis it appears that the presystemic biotransformation of tolamolol is decreased in renal failure.

Adult↗
PubMed1979

[Pharmacokinetics of a new cephalosporin, cefoperazone].

Cefoperazone is a semi-synthetic cephalosporin for parenteral use with an extended antibacterial spectrum covering Pseudomonas aeruginosa, Enterobacter cloacae and Serratia marcescens. Its pharmacokinetic properties were studied in 8 healthy subjects after 2 intravenous infusions of 2 g of the drug at a 12-hour interval. The mean peak serum concentrations were 134 +/- 16 microgram/ml and 143 microgram/ml. Cefoperazone was shown to possess a long half-life for a cephalosporin (1.7 hours). In our concentration range the drug is 90% protein bound. The apparent volume of distribution was a mean 11.4 liters and the renal clearance 18 ml/min. The cumulative urinary excretion was small, viz. 23% in 12 hours, indicating that there should be no need to modify the dosage regimen in renal failure. Comparison of in vitro studies with the pharmacokinetic properties show that 2 g cefoperazone given intravenously twice a day should inhibit most sensitive bacteria.

Bacteria↗
PubMed1979

[Value and limits of urinary protein electrophoresis with sodium dodecyl sulfate in the evaluation of glomerular nephropathies].

Qualitative analysis of urinary proteins is contrasted with histological findings of 45 renal biopsies performed in patients with chronic glomerulonephritis. Compared to electrophoresis on cellulose acetate and immunoelectrophoresis, a method using polyacrylamide gel after sodium dodecylsulfate treatment makes for more refined and objective differentiation of protein abnormalities. On the whole, proteinuria of the selective glomerular or physiological type predominates in the event of minimal change or membranous lesions. The non-selective type is found more frequently with diffuse proliferative or membranoproliferative glomerulonephritis (p less than 0.025). There are, however, too many exceptions to this rule to allow certainty, and a precise diagnosis of the particular type of glomerulonephritis is thus only possible histologically. Each type of histological involvement may cause almost any of the qualitative abnormalities of proteinuria. On the other hand, qualitative analysis of urinary proteins is useful for the detection of glomerulonephritis. A glomerular type of proteinuria may sometimes reveal involvement of kidneys at a time when, quantitatively, there is no proteinuria. In cases of orthostatic proteinuria a persistent glomerular type of tracing in recumbency suggests an organic kidney ailment. All patients in this series had a glomerular type of proteinuria when excretion was pathological, thus allowing a distinction from pure tubular involvement. 10 patients of the group, however, although they clearly had glomerular lesions (3 were diffuse proliferative glomerulonephritis) showed perfectly normal proteinuria both quantitatively and qualitatively. This was the case in systemic lupus erythematosus where kidney biopsy was performed without clinical suspicion of renal involvement. In summary, qualitative abnormalities of proteinuria call attention to underlying glomerulonephritis, although no distinction can be made between the various forms and there may be no detectable abnormality even in the event of major kidney involvement.

Adolescent↗
PubMed1979

[Cholestyramine and digoxin intoxication: therapeutic efficacy?].

Plasma levels of digoxin were measured in a patient after massive intoxication. Pharmacokinetic analysis of the data as compared with other cases of digoxin intoxication reveals that in these situations oral administration of cholestyramine may be of benefit to the patient.

Cholestyramine Resin↗
PubMed1979

[The hand in diabetes. Study of 97 diabetics compared to a control group].

To determine whether there is hand involvement specific to diabetes, 97 diabetics were compared with the same number of matched controls. Hands were examined with particular emphasis on skin, intrinsic muscles, articular mobility, sense of touch and vibration, digital systolic pressure, and radiological analysis of bones and joints. The most significant involvement, clearly present in 7 cases and less specifically in 12 other diabetics, included all of the following: atrophy and weakness of intrinsic muscles, painful interphalangeal rigidity limiting extension or flexion of the fingers, periarticular swelling of the phalanges, and trophic changes of the skin. Separately, these changes are not specific to diabetes: in the control group, although less frequent, they were found in patients aged 60 and over and are considered to be signs of senescence. Diabetes apparently accelerates the process of aging. Diabetic changes in the hand appear to be facilitated by neuropathy but not by arterial involvement. X-ray revealed a higher incidence of osteopenia and above all of vascular calcifications in the diabetic.

Adult↗