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Biomedical subjects

J Barre

Publications and source records attributed to J Barre.

At least 37 records · Page 2Linked to original sources
PubMed1991

Lack of a relationship between the polymorphism of debrisoquine oxidation and lung cancer.

1. Determination of debrisoquine oxidation phenotype was carried out in 119 healthy subjects, 135 patients with chronic bronchitis and 153 patients with lung cancer, all of Caucasian origin. 2. A non-Gaussian distribution of the log D/HD ratio was observed in the three groups. 3. Assuming an antimode of 1.12, the proportion of PMs was found to be 6.7% in healthy subjects, 8.9% in chronic bronchitics and 6.5% in patients with lung cancer. These differences were not significant. 4. The presence of a lung tumour itself had no influence on phenotype in a group of 14 patients who were phenotyped before and after surgery. 5. We conclude that a link between debrisoquine phenotype and lung cancer is unlikely.

Adult↗
PubMed1990

Effects of age on plasma protein binding of sufentanil.

The plasma protein binding of sufentanil has been studied in newborns, infants (0.5 +/- 0.3 yr), children (6.8 +/- 3.0 yr), and adults (39.5 +/- 9.0 yr). Binding of sufentanil was determined in vitro by equilibrium dialysis, and radioactive tritiated sufentanil was used for the determination of drug concentrations in plasma and buffer. The free fraction of sufentanil was significantly higher in the newborn (19.5 +/- 2.7%; P less than 0.01) than in the other age groups. The free fraction was also significantly higher in infants (11.5 +/- 3.2%; P less than 0.01) than in children (8.1 +/- 1.4%) or in adults (7.8 +/- 1.5%) but did not differ significantly between children and adults. The free fraction of sufentanil was strongly correlated with the alpha 1-acid glycoprotein plasma concentration (r = -0.73; P less than 0.001) whereas it was weakly correlated with albumin plasma concentration (r = -0.35; P less than 0.05). These data suggest that the lower concentration of alpha 1-acid glycoprotein in newborns and infants probably accounts for the decrease in protein binding of sufentanil in these age groups when compared with that in older children or adults. The increased free fraction in the neonate might contribute to the enhanced effects of lipophilic opioids in the neonate.

Adult↗
PubMed1989

Effect of Ginkgo biloba extract on microsomal enzyme induction.

Twenty-four healthy volunteers were divided in three groups who were randomly assigned different treatments for 13 days: group I received 400 mg/day of a defined Ginkgo biloba extract (GBE), group II 300 mg/day of phenytoin and group III a placebo. The elimination half-life of antipyrine was measured with a high performance liquid chromatographic technique initially and on the last day of the administration of the treatments. The results show that the half-life of antipyrine was not affected by GBE and placebo treatments, whereas it was significantly decreased (p less than 0.05) frm 12.2 to 6.8 h after phenytoin control treatment. This study demonstrates that GBE has no effect on the hepatic microsomal drug oxidation system.

Adult↗
PubMed1988

Pharmacokinetics of veralipride after chronic administration in humans.

A pharmacokinetic study of veralipride (N-[(1-allyl-2-pyrroli dinyl)methyl]-5-sulfamoyl-o-veratramide) was performed in healthy volunteers during a chronic administration. The pharmacokinetic model based on the hypothesis of a double site for drug absorption, previously used after a single-dose oral administration, was developed to fit the data obtained after chronic administration. The empirical model used allows correct depiction of the behavior of the drug in the body, especially secondary peaks. According to the results, veralipride pharmacokinetics did not show any change upon chronic administration.

Adult↗
PubMed1988

Problems in therapeutic drug monitoring: free drug level monitoring.

Historically, it has been assumed that only free drug concentration is the pharmacologically active species. This article reviews the theoretical pharmacological and pharmacokinetic justifications for monitoring free drug levels. The determinants likely to influence plasma protein binding and the free concentrations of drugs are delineated. The different methods which can be used for determining free drug level are presented. Their advantages and drawbacks as well as their reliability and suitability for routine clinical practice are discussed. Currently, antiepileptic drugs such as valproic acid, phenytoin, carbamazepine and a few antiarrhythmic drugs meet the theoretical criteria justifying free drug level monitoring. Conditions causing alteration in free concentrations of these drugs are reported. But, for all these drugs, there is a considerable lack of data establishing the correlations between therapeutic or toxic response and free concentration. Presently, our capability to interpret correctly the free drug level data is still limited. In the future, much more effort must be devoted in order to provide sufficient information on the clinical relevance of free drug concentration.

Anti-Arrhythmia Agents↗
PubMed1988

Blood binding and tissue uptake of drugs. Recent advances and perspectives.

The free drug hypothesis, which states that only the unbound moiety of drug in blood is available for tissue diffusion, is discussed according to recent investigations. In some experimental conditions, it must be assumed that part of the protein-bound drug in plasma is extracted during a single passage through the organ studied. The mechanisms underlying these observations are not unequivocal and remain hypothetical. In the liver, high-affinity binding sites for serum albumin have been demonstrated, and they would explain the high extraction by liver of endogenous and exogenous compounds. However, these experiments measure the unidirectional transfer of a drug from the vascular to the extravascular space in non-steady-state conditions. Hence, in steady-state conditions, the free drug hypothesis cannot be ruled out because it is supported by numerous pharmacokinetic studies.

Animals↗
PubMed1988

Pharmacological criteria for risk-benefit evaluation of NSAIDs.

Evaluation of new non-steroidal anti-inflammatory drugs (NSAIDs) must compare efficacy and toxicity with existing compounds. Real progress involves maintaining effectiveness while decreasing toxicity. It is relatively easy to assess the effects of NSAIDs in animal models, and to determine gastrointestinal toxicity. However, although the ratio of active and toxic doses in animals can be extrapolated to man, the approach is limited and the NSAID needs to be assessed in a clinical setting as early as possible. In France, a national survey system has reported a wide range of adverse effects related to NSAIDs and shown important differences between compounds. Overdosage may be one of the factors responsible for toxicity, therefore pharmacokinetic evaluation is useful. In some disease states e.g. rheumatoid arthritis, there is a higher possibility of saturation pharmacokinetics with some drugs. Other pharmacokinetic parameters of interest are half-life, functions limiting activity, and hepatotoxicity. Furthermore, different pharmacokinetic parameters are required for different forms of disease. In acute states, the NSAID should have a short half-life and low protein binding and vice versa in chronic states. An important goal is to develop more selective NSAIDs regarding mechanisms of action or distribution into diseased tissues.

Animals↗
PubMed1988

Distribution of cyclosporin A between blood cells and plasma of cardiac and renal transplant recipients.

The relationship between blood cells and plasma concentrations of cyclosporin A (Cy A) determined by radioimmunoassay, was investigated in 12 heart and 12 kidney transplant recipients. The decision between a linear and nonlinear model was made according to a standardized residuals plot. We observed high blood cells-plasma concentration ratios in the two groups, indicating a high affinity of Cy A for blood cells. The distribution of Cy A between blood cells and plasma was ascribed to a nonlinear saturable model in the two groups. According to our results we have simulated the blood-plasma concentration ratio of Cy A as a function of plasma Cy A concentration and hematocrit.

Adolescent↗
PubMed1988

Plasma and tissue binding as determinants of drug body distribution. Possible applications to toxicological studies.

1. Drugs are distributed through all body tissues via blood circulation. Consequently, most drugs rarely elicit one specific pharmacological effect but more generally have several, in different tissues. 2. In other words, drug effects are not unique or isolated, because drug distribution is not selective. Thus, considering a drug with a given liposolubility, its quantitative distribution in the body may be predicted in taking into account the physico-chemical properties of the compound and the blood flows and the lipid contents of the different tissues and organs it will reach. 3. This paper attempts to show that plasma binding can influence the tissue distribution of drugs and may be applied to the minimization of toxic effects by decreasing the amounts of drug reaching the relevant tissues. 4. The value of an early determination of drug binding in human blood will be emphasized. This is justified by the fact that tissue distribution of drugs does not vary greatly between species whereas plasma binding may show important inter-species differences. Thus different plasma binding in humans may lead to large variations in tissue distribution as compared with experimental animals.

Animals↗
PubMed1988

[Value of cyclosporin A in dermatomyositis in a child].

Cyclosporin A was used in a 3 1/2 year-old child with dermatomyositis exhibiting severe junctional impairment and intolerance to steroids. After a few weeks, marked clinical improvement was observed allowing a reduction of the doses of steroids. After 9 months, the clinical status was satisfactory: the calcifications had lost their inflammatory characteristics. No side effect of cyclosporin A was observed at the dose used (4.4 mg/kg/d) which maintained effective blood concentrations between 80 and 220 ng/ml.

Child, Preschool↗
PubMed1987

Binding studies of macrolides, lincosamides and streptogramins to Streptococcus G group using [3H]-erythromycin.

Parameters of [3H]-erythromycin binding to Streptococcus are determined in vivo using both equilibrium and kinetic methods. This binding is saturable, reversible and independent of energetic systems. Whatever the methods used, the binding parameters are identical as 14 nM for the dissociation constant of the complex erythromycin-Streptococcus and a density of binding sites of 11,865 molecules/cell. Other macrolides, streptogramins and lincosamides competitively displaced bound [3H]-erythromycin suggesting that these compounds share common binding sites on the bacteria. In parallel, the MIC values of these antibiotics against Streptococcus are determined by agar dilution method in Mueller-Hinton medium with 5% of horse blood in order to compare the binding and microbiological parameters. A strong correlation (n = 0.863) has been found between the corresponding inhibition constants and MIC values. Such binding studies could be used in conjunction with microbiological assays for primary screening of active analogous or other compounds with interfere with [3H]-erythromycin binding to the bacteria.

Anti-Bacterial Agents↗