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Biomedical subjects

B Flouvat

Publications and source records attributed to B Flouvat.

At least 91 records · Page 5Linked to original sources
PubMedDate not supplied

Influence of food on the absorption of theophylline administered in the form of sustained release tablet and microgranules.

Two sustained-release formulations of theophylline, tablets (T) and microgranules (MG) forms, were administered in a randomized order to 8 healthy subjects in fasting or with a high-protein test meal (50 per cent). Blood was collected for 32h post-dose. In fasting subjects, absorption of theophylline was significantly faster for T (tmax 5 h) as compared with MG (tmax 8 h, p less than 0.05), but Cmax and AUC were comparable; intersubject variability was higher with T. Administration of a high-protein test meal with T produced a significant decrease of the zero-order absorption rate constant of theophylline (K omicron 37.8 +/- 9.1 mgh-1 after meal versus 58.8 +/- 13 mgh-1 in fasting, p = 0.01), tmax was doubled to 10 h, and Cmax increased by 25 per cent (6.33 +/- 2.16 mgl-1 versus 5.04 +/- 1.28 mgl-1, p less than 0.02); with MG, tmax were the same (8 h), Cmax were not significantly increased (4.79 +/- 0.84 mgl-1 versus 4.55 +/- 0.67 mgl-1), absorption was delayed (lag-time 1.28 +/- 0.58 h) and the absorption was slightly accelerated (K omicron 50.4 +/- 10.4 mgh-1 versus 42.3 +/- 11.9 mgh-1, NS). For each form bioavailability was not significantly modified by food. This study demonstrated that food rich in protein modifies the absorption rate of theophylline in a sustained-release tablet formulation but is without influence in a pH-independent, sustained-release microgranule formulation.

Administration, Oral↗
PubMedDate not supplied

Binding of cefalotin to human serum albumin.

Binding of cefalotin to human serum albumin was studied in vitro by equilibrium dialysis and the quantitative measurement of cefalotin was made by fluorimetric assay. The binding rate of cefalotin to human serum albumin found to be 61,1%. The determination of drug binding parameters showed a large number of binding sites (n = 9.36) and a moderate affinity (K = 3898 M-1).

Cephalothin↗
PubMedDate not supplied

Clinical pharmacology of prazosin in hypertensive patients with chronic renal failure.

The clinical pharmacology of prazosin was studied in 10 hypertensive patients with chronic renal failure (group I) and in 9 hypertensive patients with normal renal function (group II). Prazosin, 2 mg, was given orally and blood samples were drawn at intervals for spectrofluorimetric assay. Blood pressure and heart rate were obtained at the same time. In the renal failure group, prazosin induced a significant decrease in systolic and diastolic blood pressures (-19 and -23%, respectively) at 90 min after intake, and these alterations were more rapid and marked than in the normal renal function group. Peak plasma concentration (Cmax) was higher (33.5 +/- 3.7 vs. 20.04 +/- 1.7 micrograms/liter, p < 0.01) and occurred earlier (1.3 +/- 0.2 vs. 2.7 +/- 0.3 hr, p < 0.005) in group I than in group II. The area under the plasma concentration-time curve (AUC0 infinity) was increased in the renal failure group (206.1 +/- 31.1 vs. 112.4 +/- 9.4 micrograms/hr/liter, p < 0.01). Apparent plasma elimination half-life (t 1/2) was not significantly different in the two groups (3.6 +/- 0.4 vs. 2.9 +/- 0.3 hr. ns). The mean blood pressure change (delta MBP%) was significantly correlated with the plasma level of prazosin in the renal failure group (n = 97, r = 0.489, p < 0.001) but not in patients with normal renal function (n = 74, r = 0.297, ns). The hypotensive action of prazosin is greater in patients with chronic renal failure, and the bioavailability or distribution of the drug is altered. Therefore, prazosin dosages should be modified in patients with impaired renal function.

Adult↗
PubMedDate not supplied

Clinical pharmacology and pharmacokinetics of prizidilol in hypertensive patients.

We evaluated the clinical pharmacology of prizidilol, a compound with vasodilator and beta-blocking properties, in 12 hypertensive patients with normal renal function. A single dose of 600 mg prizidilol was given orally and blood samples were withdrawn at intervals for high-performance liquid chromatography assay. Blood pressure and heart rate were recorded every hour in supine and standing positions. A nitroglycerin test was performed at the 2nd, 4th, and 6th h for evaluation of cardiac beta-adrenoceptor activity. Results were compared with those after placebo intake the day before. Prizidilol produced a significant decrease in supine systolic and diastolic blood pressures (-22 and -24%, respectively), with a maximum effect 5 h after intake. Blood pressure changes were not different in slow and fast acetylators, suggesting that the acetylated metabolites were active. Heart rate decreased slightly but significantly during the first 2 h, but was similar to control levels thereafter. However, the nitroglycerin test data suggested a prolonged blockade of beta-adrenoceptor activity. Pharmacokinetics showed large variations among patients; several peaks were observed on the curves, indicating irregular absorption. The apparent plasma elimination half-life was 4.4 +/- 0.4 h. Total body clearance was high despite a very low renal clearance, indicating that the drug was eliminated mainly by the metabolic or intestinal route. No significant correlations were found among plasma concentration, blood pressure, and heart rate. In conclusion, prizidilol is a potent antihypertensive drug having equilibrated vasodilator and beta-blocking effects. The pharmacokinetic data suggest a first-pass effect and elimination by extra-renal routes.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

[Simultaneous quantitative determination of amprenavir and indinavir in human plasma by high-performance liquid chromatography].

A reversed-phase high-performance liquid chromatographic assay for the determination of the HIV protease inhibitors amprenavir (Agenerase) and indinavir (Crixivan) in human plasma is described, using a mobile phase consisting of 0.50 M phosphate buffer (adjusted to pH 5,5) - Milli-Q water - acetonitrile (120: 1,080: 800, v/v/v). A solid-phase extraction using C18 extraction columns (Discovery columns 100 mg, 1 ml Supelco) and a liquid-liquid extraction with 0.5 ml hydrogenocarbonate/carbonate buffer (adjusted to pH 10.6) and 6 ml methyl ter-butyl ether have been compared. The liquid-liquid extraction has been chosen to be easier and cheaper. The method has been validated over the range of 60 to 3,000 ng/ml for amprenavir and 20 to 3,000 ng/ml for indinavir using a 0.5 ml sample volume. The specificity, linearity, accuracy and precision have been studied. The limit of detection was respectively for amprenavir and indinavir 15 and 4 ng, and the limit of quantification was 60 and 20 ng/ml. Stability tests under various conditions were performed. This assay can readily be used in a hospital laboratory for the routine monitoring of plasma concentrations of amprenavir in HIV-infected patients. The trough plasma concentrations average has been determined in patients treated by amprenavir and indinavir for seven months.

Anti-HIV Agents↗
PubMedDate not supplied

[Emergency toxicology: analytic protocol applicable to biolobic media in tentative autolysis].

Here is exposed a method to detect and identify, without delay and in biological media, toxic substances generally found when attempting autolysis. It implies: 1; coloured reactions performed directly or after having isolated the substances using organic solvants, 2; thin layer chromatographies of these extractums which are developed and revealed in very precise conditions. Techniques for titration of some drugs are exposed. 253 cases of toxic coma have been studied, and the results of this inquiry analysed, more particularly cases induced by barbiturates.

Autolysis↗
PubMedDate not supplied

[Biomarkers for toxicity and metabolic abnormalities of the main severe poisonings. Clinical and toxicologic symptoms. Conservative determination].

The members of the joint group "Toxicology and Clinical Biology" of the French Society of Clinical Biology (SFBC), the French Society of Analytical Toxicology (SFTA), and the Society of Clinical Toxicology (STC), suggest guidelines to meet the requirements of clinical biologists who are not specialized in toxicology. Based on good laboratory practice they propose a number of guidelines. Three synthetic tables have been established. They are not only toxicity biomarkers and metabolic disorders associated with the main severe intoxications, but also clinical signs that are observed during these intoxications, finally biological sampling as a precautionary measure. The table also takes into account approximately fifty xenobiotics: main clinical signs emergency, identification or quantification of the suspected product, useful biological markers, therapeutic, quantitations necessary to take into consideration patient care, and poison antidotes, are described. Recommendations regarding medical and forensic techniques are also proposed by the group. It is also necessary to collect and store biological samples when the individual patients are in charge. These samples will be analyzed or not depending on the individual case history.

Biomarkers↗
PubMedDate not supplied

[Methods of cyclosporine determination in biological media].

Cyclosporine is an immunosuppressive medicine widely used in all grafts and organ transplantations. Its pharmacokinetic characteristics, especially its intensive metabolism, result in great variability potential between and within patients justifying blood levels' determination in patients treated with this drug. If the biological medium (whole blood) selection is of the utmost importance regarding the quality of the result and its validity, the accuracy of the result compared to the blood levels of the drug will depend on the selection of the determination technic involved. At present, various analytical methodologics are available: the immunological technics involving radioactive or non-radioactive tracers, and HPLC (High Performance Liquid Chromatography) technic. The latter requires good chromatography experience; it takes more time to be implemented due prior extraction of cyclosporine from the biological media. This extraction can be effected with organic solvents or by column chromatography: these various technics will be discussed and compared. This methodology enables one to determine metabolite concentrations. Regarding immunological technics, multiclonal or monoclonal antibodies are available for technics involving fluorescence polarization. However, for radioactive tracings and enzymic tracers, only one specific antibody is available. It is important to take into account the specificity of these antibodies relative to the various metabolites regarding results interpretation, their crossing rate being altered in accordance with antibodies and related pathologies. The validity of these technics will be discussed in words of accuracy and exactitude. The laboratory arrangement, the feasability and cost of the technic are also factors to be taken into consideration. At present selection tends towards to most specific technics.

Biological Assay↗
PubMedDate not supplied

[Pharmacokinetics of drugs in children].

The pharmacokinetic parameters of a drug allow to define its posology. The large physiological modifications, which occur during the development of a child from birth to adolescence, can intensely modify some pharmacokinetic parameters of a drug and so increase its toxicity or inhibit its activity. In this review, pharmacokinetic consequential effects of child development are studied and discussed with regard to some examples.

Child↗
PubMedDate not supplied

Hemodynamic effects of a new antiarrhythmic agent: cibenzoline.

The hemodynamic effects of an intravenous dose of 1 mg/kg of Cibenzoline, a new anti-arrhythmic agent with properties of classes I, III and IV of the Vaughan-Williams classification, were studied in 9 patients during routine cardiac catheterization. Six patients had valvular heart disease (aortic insufficiency in 5 and mitral stenosis in 1), one patient had ischemic heart disease, one patient had alcoholic cardiomyopathy and the remaining patient had coarctation of the thoracic aorta. Left ventricular pressure and right sided intracardiac pressures were recorded using a high fidelity transduced and a Swan-Ganz catheter respectively. The first derivative of the left ventricular pressure was obtained electronically and Vmax calculated by linear extrapolation to zero load of the contractile element shortening velocity--left ventricular pressure relationship. Plasma levels of Cibenzoline were measured by gas liquid chromatography. All these parameters were obtained under baseline conditions and then 5, 10, 20, 40 and 60 minutes after intravenous administration of Cibenzoline. Cardiac index fell by 20% 5 minutes after the injection of Cibenzoline, and returned to control after one hour only. This fall was primarily related to a decrease in stroke index, since heart rate remained virtually unchanged. Right and left ventricular filling pressures increased significantly from the 5th to the 40th minute. Aortic systolic pressure fell by approximately 6%, without any change in mean and diastolic aortic pressures. Peripheral and pulmonary resistances increased at 20 minutes by 33% and 45%, respectively. Left ventricular peak positive dP/dt and Vmax decreased significantly at 5 minutes and remained below the baseline value until 60 minutes by 9% and 11% respectively. Percent changes in cardiac index, dP/dt and Vmax were significantly correlated to cibenzoline plasma levels (r = 0.85, 0.79, 0.74 respectively; n = 45). Thus, doses achieving plasma levels within the reported therapeutic range (250-350 ng/ml) would be expected to result in a 8-12% decrease in cardiac output associated with 12-17% and 15-21% reduction of left ventricular dP/dt and Vmax respectively. These data indicate that cibenzoline exerts significant negative inotropic effects. Its use in the subset of patients with severely depressed ventricular function warrants caution.

Adult↗