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Biomedical subjects

L Balant

Publications and source records attributed to L Balant.

At least 109 records · Page 6Linked to original sources
PubMed1970

Perifusion of rat pancreatic tissue in vitro: substrate modification of theophylline-induced biphasic insulin release.

The immunoreactive insulin (IRI) release patterns produced by continuous theophylline stimulation of rat pancreas have been defined, using an in vitro perfusion system. In the presence of glucose, citrate, and pyruvate at concentrations which were nonstimulatory by themselves, continuous stimulation with theophylline produced a biphasic IRI release profile. In the absence of substrate, continuous theophylline stimulation produced only an abrupt and limited primary response. Of the substrates tested, only glucose significantly enhanced this primary response. With increasing theophylline concentrations, whether in the presence or absence of substrate, significant increases were noted in the primary response as estimated by either the maximum rate of IRI release attained or by the total amount of IRI released during this time. Similarly, the secondary responses to theophylline increased with theophylline concentration in the presence of either citrate or pyruvate. With glucose as substrate, however, increasing theophylline concentrations from 2.5 to 5, then 10 mM produced a progressive reduction in both indices of the secondary response, which was inversely related to the primary response. These findings suggest that cyclic AMP not only mediates IRI release in quantitative terms but is also implicated in the qualitative nature of the response pattern. They also indicate a possible metabolic basis for biphasic IRI release, the acute or primary response being dependent upon the basal state of the cell and the availability of endogenous energy sources, the secondary response upon the availability of exogenous substrate.

Adenine Nucleotides↗
PubMedDate not supplied

The genetic control of bufuralol metabolism in man.

Bufuralol (Ro 3 - 4787, Angium) is a non selective beta-adrenoceptor blocking drug with some degree of sympathomimetic action and a longer duration of action than propranolol. Plasma concentrations of bufuralol and 1'-hydroxybufuralol, its main blood derivative which shows similar beta-adrenoceptor blocking properties, were determined in healthy volunteers after a 60 mg oral and a 20 mg intravenous dose. Peak plasma concentrations were higher for the parent drug but due to a longer elimination half-life, the metabolite concentrations became higher after a few hours (bufuralol t 1/2 = 2.7 +/- 0.9 h, metabolite t 1/2 = 6.1 +/- 1.5h). The bioavailability of the tablet tested was 46 +/- 15%. The occurrence of side-effects in a subject with abnormal pharmacokinetics of the drug in this study and in a previous study with this drug suggested the possibility of a pharmacogenetic anomaly. Determination of the plasma metabolic ratio in the family of this subject and in a larger population confirmed that aliphatic hydroxylation of bufuralol is under polymorphic control. Phenotyping of our volunteers with debrisoquine showed the present pharmacogenetic anomaly to be the same as the one reported for debrisoquine alicyclic hydroxylation. The occurrence of side-effects in poor metabolizers as seen with bufuralol illustrates the clinical relevance of the hydroxylation polymorphism. In Switzerland the frequency of poor metabolizers is about 9% as previously reported for caucasian British subjects.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Differences in kinetic properties of drugs: implications as to the selection of a particular drug for use in patients with renal failure with special emphasis on antibiotics and beta-adrenoceptor blocking agents.

Adjustment of dosage of a renally excreted drug (or active metabolite) for patients with severe renal failure still causes some difficulties. It is therefore helpful to select, within a given therapeutic group of drugs, a compound that is particularly safe and easy to use and, if possible, does not require adjustment of dosage. This is 'the drug of choice for renal patients'. Such a drug would ideally meet the following pharmacokinetic criteria: normal urinary excretion less than 30% of the administered dose, predominant biliary and intestinal removal, disposition essentially unaffected by parameters likely to be modified in renal failure (e.g. changes in serum proteins or fluid compartments: receptor sensitivity, etc), and pharmacokinetics not complicated by the formation of active or toxic metabolites that depend on urinary elimination. Above all, the drug should have a wide therapeutic margin and must be free of nephrotoxicity. Examples of drugs of choice for patients with impaired renal function are given for some important therapeutic groups and special emphasis is placed on antibiotics and beta-adrenoceptor blocking agents.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Clinical pharmacokinetics of the third generation cephalosporins.

At the present time, the third generation cephalosporins that are already on the market or close to this point include cefsulodin, cefotaxime, cefoperazone, latamoxef, ceftriaxone, ceftazidime, ceftizoxime and cefotetan. Other newer compounds are also under development but have not been included in this review. None of the third generation compounds is suitable for oral administration and, accordingly, their pharmacokinetics have been studied only after intravenous and intramuscular administration. Microbiological assays and HPLC methods have been used for the measurement of plasma/serum, urine, bile and cerebrospinal fluid (CSF) concentrations. As found with cefotaxime, microbiological assays should only be used when the full metabolite spectrum of a particular drug is known, as otherwise, the presence of microbiologically active metabolites may lead to erroneous conclusions. Under normal conditions, the major route of elimination is via the kidneys for cefsulodin, latamoxef, ceftazidime, ceftizoxime and cefotetan. In contrast, cefoperazone is mainly eliminated in the bile, whereas cefotaxime and ceftriaxone depend both on the liver and the kidneys for their elimination. With the exception of ceftriaxone, which has a longer elimination half-life (i.e. around 8 hours), all the other third generation cephalosporins have a t1/2 ranging between 1.5 and 2.5 hours. Plasma protein binding is variable from one compound to another. However, the clinical relevance of this parameter is not clearly established since tissue penetration also depends on the relative affinity of the drug for tissue components. Third generation cephalosporins seem to penetrate adequately into the CSF and, thus pharmacokinetically appear to be appropriate agents for the treatment of meningitis. The degree of modification of pharmacokinetic parameters by renal insufficiency or hepatic diseases depends, as for other drugs, on the extent to which the compound is excreted via the kidneys or the liver. The third generation cephalosporins have been extensively studied under these conditions and recommendations for dosage modification in special circumstances are available for most of them. The pharmacokinetics of some third generation cephalosporins may be modified in neonates and elderly patients. Accordingly, their use at the extremes of age must be accompanied by a closer than usual clinical monitoring of the patient. From a clinical point of view, the third generation cephalosporins possess reliable pharmacokinetic properties.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

[Pharmacokinetic perturbations in kidney failure. Anomalies of metabolites and tissue diffusion (author's transl)].

Complex pharmacokinetic perturbations follow kidney failure. Delayed excretion affects not only the original substance but also metabolites, as illustrated by the behaviour of glipizide and glibenclamide. Moreover, abnormal absorption, distribution, and metabolism of these drugs also often occur and are particularily evident for some beta-blocking agents. Analysis of tissue pharmacokinetics shows that aminosides accumulate in the renal cortexand persist there for several months. This phenomenon is markedly enhanced in acute obstructive kidney failure and largely accounts for the nephrotoxicity of these drugs.

Absorption↗