Search PubMed⌕ Search

Biomedical subjects

C Brunet

Publications and source records attributed to C Brunet.

At least 181 records · Page 10Linked to original sources

Antioedematous properties of benzoxazolinone-beta-amino-ketones.

Four chemically related benzoxazolinone-beta-amino-ketones act in vitro on the guinea pig ileum as histamine, serotonin, bradykinin and prostaglandin antagonists. These compounds decrease the rat carrageenan-induced paw oedema mediated by the above-mentioned mediators. With the aim of bringing out the acting mechanisms of that inhibition we studied their ability to inhibit various models of oedema induced either by the release or the injection of the involved mediators. It seems that there is a good enough correlation between the former results obtained in vitro and the present results.

Animals↗

A routine HPLC method for monitoring midazolam in serum.

A routine high-performance liquid chromatographic method for measuring midazolam in human serum has been developed. The sample preparation procedure consisted of simple liquid-liquid extraction with dichloromethane, followed by evaporation under nitrogen. The mobile phase used was a mixture of acetonitrile at 0.02 M and sodium acetate at pH 3.0 (80:20, v/v) and a flow-rate of 1.2 mL/min. The separation was performed on two cyanopropyl columns (150 x 4.6 mm). The detection was by UV absorption at 240 nm. A linear range from 10 to 1,000 ng/mL and a quantification limit of 7.4 ng/mL of serum was reached. The mean intra-assay and inter-assay reproducibility from serum sample spiked with 100 ng/mL were 4.1 and 4.7%, respectively. The recoveries from serum sample spiked with 50, 100, 500 ng/mL were 85.46, 85.38 and 85.57%, respectively. This method was developed to allow pharmacokinetics study of midazolam in young patients in short surgical interventions.

Chromatography, High Pressure Liquid↗

Determination of cyclohexamone after derivatization with 2,4-dinitrophenyl hydrazine in intravenous solutions stored in PVC bags by high performance liquid chromatography.

A high performance liquid chromatographic procedure is described for the determination of cyclohexanone leached in intravenous solutions from the poly(vinyl chloride) bags. After derivatization with 2,4-dinitrophenylhydrazine and extraction with pentane, the cyclohexanone derivative was analysed on a C18 BDS Hypersil column using mobile phase mixture of acetonitrile:water (55:45). Ultra-violet detection was performed at 368 nm. The limit of quantification was 30 ng/mL and the assay was linear from 0.05 to 50 micrograms/mL. The recovery was better than 95%. The proposed method is satisfactory in its accuracy and precision with particularly relative standard deviations (RSD) for intra-assay and inter-assay of below 10%. This method has been successfully used for the determination of cyclohexanone in aqueous solutions such as sodium chloride (0.9%) and glucose (5%) stored in PVC containers. The values obtained varied between 2.04 and 44.9 micrograms/mL according to solutions and volume.

Chromatography, High Pressure Liquid↗

Solid phase extraction and high performance liquid chromatographic determination of dobutamine in plasma of dialysed patients.

An isocratic reversed-phase high performance liquid chromatographic method has been developed for th e determination of dobutamine in the plasma of dialysed patients. A solid phase extraction method with a Sep-Pak C18 cartridge was used to isolate the drug and isoxsuprine (internal standard) from plasma. The separation was carried out on an ODS-Hypersil column with 0.1 M phosphate buffer:acetonitrile:methanol (72:20:8 v/v/v) as the mobile phase. The recovery of dobutamine added to plasma by the extraction procedure was 87 +/- 2.3% (mean +/- SD). The accuracy and reproducibility of the method were within acceptable limits over the concentration range 0-1000 ng/mL. Quantification was by fluorescence detection at 275 nm excitation and 310 nm emission wavelengths with a detection limit of 5 ng/mL for dobutamine. This procedure was applied to ascertain the pharmacokinetics of dobutamine infusion in nine patients with cardiogenic shock and end-stage renal disease undergoing haemodialysis.

Chemical Phenomena↗

Pharmacokinetics of midazolam: comparison of sublingual and intravenous routes in rabbit.

In France, the legal routes used to administer midazolam to a patient are intravenously and intramuscularly. For anaesthetists, these routes are not well adapted to paediatric use; they lead to pain at injection site and stress on children. The sublingual route should be a good compromise between stress and quick efficiency. We have developed a sublingual tablet of midazolam. The aim of the present investigation is to compare the pharmacokinetic parameters of midazolam tablets administered by the sublingual and intravenous routes in 6 rabbits to determine the bioequivalence between these routes. We have estimated the 1-hydroxy-midazolam serum level by difference between RRA and HPLC values. By the sublingual route, midazolam absorption is substantial and fast. The statistical analysis, on data obtained with HPLC dosage, shows no significant difference between pharmacokinetic parameter values calculated after intravenous and sublingual administration (0.5 mg). The absolute bioavailability was close to 100%. With RRA dosage, however, AUCs were greater than those obtained by HPLC dosage (174%). 1-hydroxy-midazolam seems to have a great importance in BZD activity. To estimate the bioequivalence between intravenous and sublingual midazolam administration, it is necessary to take into account the active metabolites.

Administration, Sublingual↗

Acid metabolite of progabide pharmacokinetics following single administration in the rabbit with special references to HPLC and (3H) muscimol radioreceptor assay.

The aim of the present study was to monitor plasma levels of progabide and its metabolites in the rabbit following single oral administration of 20 mg.kg-1. The plasma levels were determined selectively using high performance liquid chromatography (HPLC) and then correlated with a global estimation by a (3H) muscimol radioreceptor assay (RRA). In our "in vitro" binding conditions progabide itself was virtually ineffective (IC50 greater than 100 microM) so only RRA active materiel plasma concentrations were studied. A good enough correlation (r = 0.71) has been established between HPLC and RRA plasma concentrations from 0 to 3 hours following oral administration specially considering the absorption phase. But with closed regards to the elimination pharmacokinetic parameters specially the elimination half-life values (t1/2el (RRA) = 1.67 h and t1/2el (HPLC) = 0.70 h) that correlation should be weaker than the former instead metabolites including GABAmide and GABA itself are probably present in amounts likely to affect the displacement of specific binding in the (3H) muscimol radioreceptor assay.

Animals↗

Induction of propranolol metabolism in isolated rats hepatocytes treated by di(2-ethylhexyl) phthalate (DEHP) and mono(2-ethylhexyl) phthalate (MEHP).

Blood lines of polyvinyl chloride (PVC) for hemodialysis usually contain di(2-ethylhexyl) phthalate (DEHP) as a plasticizer. Previous studies show that 1 mg/kg of this plasticizer can leach into the blood during one dialysis session. It is rapidly metabolized in the liver. Mono(2-ehtylhexyl) phthalate (MEHP), its main metabolite can be detected as well. After oral administration to rodents, both compounds caused a variety of adverse biological effects such as testicular atrophy, peroxisome proliferation and hepatic peroxisomal enzyme induction. Male wistar rats were treated intraperitoneally by DEHP and MEHP using twice the dose of that involved in human exposure during a dialysis session. Propranolol metabolism by hepatocytes was investigated after fresh isolation from treated and untreated rats by means of reverse phase HPLC. The choice of propranolol as a substrate was made because of its rather quick liver metabolisation. Phenobarbital was chosen in the study as a reference of enzymatic inducer to evaluate the inducing effect of DEHP and MEHP. Propranolol was metabolized by the hepatocytes of both treated and untreated rats. Hepatocytes isolated from rats treated by phenobarbital, MEHP and DEHP were shown to have a higher speed constant of metabolism indicating a rapid metabolism of propranolol. Under these conditions, in fact, propranolol metabolisation was found to be respectively 6, 2.7, 2 times faster than the propranolol metabolisation of untreated rats. The hypothesis that DEHP and MEHP are enzymatic inducers, particularly cytochrome P450 (CYP) inducers of the xenobiotics metabolism on the intact liver after IP administration has become been found to be valid. The results obtained in this study confirm the value of isolated hepatocytes as an in vivo drug metabolism predictive model.

Animals↗

[Two stage videoassisted restorative proctocolectomy. Early experience of 12 cases].

AIM OF THE STUDY: This study reports our early experience in two-stage video assisted restorative proctocolectomy (RPC). PATIENTS AND METHODS: From May 1999 to May 2003, 12 video assisted RPCs were performed (mucosal ulcerative colitis: n = 11; familial adenomatous polyposis: n = 1). These patients were matched for age, gender, body mass index and indication for surgery, with 12 patients who underwent RPC by laparotomy (open group). RESULTS: Median operative time was significantly longer in the video assisted RPC group (400 min; range: 360-490) vs open group (300 min; range: 210-390) (P = 0.003). A conversion in midline laparotomy (under the umbilicus) was necessary in 3/12 patients (25%) in the video assisted RPC group. Return to bowel function and oral intake occurred two days earlier after video assisted RPC (respectively, P = 0.009 and P = 0.0001) but length of stay was not significantly shorter in this group. A complication occurred in 3/12 patients (25%) in both groups, which lead to a reoperation in one patient in the open group (ns). CONCLUSION: Two-stage videoassisted RPC is feasible at the cost of a lengthening of operative time, Nevertheless postoperative results after video assisted RPC are comparable to those obtained after RPC by laparotomy.

Adenomatous Polyposis Coli↗