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Biomedical subjects

J P Dubois

Publications and source records attributed to J P Dubois.

At least 19 recordsLinked to original sources
PubMed1995

[Legal and economic aspects of peritoneal dialysis].

Treatment of renal insufficiency is, in it principle, covered by "hospital law" and its decrees of application: however the regulations for these methods of treatment only concern hemodialysis centers. CAPD is only subjected to a memorandum from the "Caisse Nationale d'Assurance Maladie" (National Medical Insurance) dated November 26, 1979, which fixes a weekly price. The text only concerns CAPD with single bag and does not deal the new methods. These new techniques are very expensive and well above the current weekly fixed price. According to a survey of the cost, carried out by AURA (Paris), during the first six months in 1992, the price of such techniques involves an average additional cost of 45% when double bags were used and 80% when APD was operated. In the long term, these techniques will result in substantial savings for the National Medical insurance scheme by reducing the risk of peritonitis and by facilitating patients' social and professional activity. However, the absence of adequate reimbursement causes running deficits and curbs development. Public Service Authorities should consider all these factors and should not forget that PD is generally cheaper than hemodialysis.

Health Care Costs↗
PubMed1994

Geostatistical analysis of soil contamination in the Swiss Jura.

The topsoil of a 14.5 km(2) region of the Swiss Jura has been surveyed to identify the distributions of trace metals in it. The soil was sampled at 366 sites selected by combining a square grid and nesting. Concentrations of seven potentially toxic metals, namely Cd, Co, Cr, Cu, Ni, Pb and Zn, were measured. Land use and geology (stratigraphy) were also recorded. Variograms were bounded in the range from 110 m to 1500 m with contributions to the variance at all distances exceeding 6 m. The variograms of Cd, Cr, Cu and Pb are dominated by short range correlation, those of Co and Ni by correlation of long range, and Zn is intermediate. The concentrations were estimated at the nodes of a fine grid by ordinary block kriging and then contoured to produce maps. The maps of Co and Ni have a coarse patchy pattern similar to that of the geology, suggesting that these metals derive from the bedrock. This is supported by analysing the variance by geology. Copper and Pb have finer patterns of distribution, and are more likely to have been added with fertilizer or manure or domestic waste. Cadmium could originate from human activities, such as smelters or fertilizer spreading, or from specific geological deposits, such as moraine.

Journal Article↗
PubMed1991

Pharmacokinetics of cadralazine in a large group of hypertensive patients chronically treated with cadralazine: advantage over a conventional study in a small group of patients.

The concentrations of cadralazine in plasma were studied in 101 hypertensive patients treated with oral doses of 10, 15, or 20 mg of cadralazine once daily. Most of the patients received additionally a beta-blocking drug (n = 87) and a diuretic (n = 52). Few blood samples were collected in each patient on several occasions during the treatment, which usually lasted for more than 6 months. No accumulation of cadralazine in plasma occurred in any of the patients and the maximum concentrations were similar to those recorded in a small sample of healthy volunteers. The terminal half-life of elimination (3.6 h) was longer than that observed in healthy subjects (approximately 2.5 h). Conversely, the total clearance (197 ml/min) was lower (285 ml/min in healthy). The half-life and the total clearance in plasma were not dose dependent. In the patients treated for more than 6 months, no change in the pharmacokinetics of cadralazine was detected. The description of the distribution of concentrations showed that one-half of the patients behaved similarly to healthy subjects concerning half-life and total clearance. The other half presented a slower elimination of the drug (t 1/2 = 4.4 h and ClT = 130 ml/min) and these patients were significantly older (p = 0.01) than the former. This suggests that special attention should be paid to old hypertensive patients when a dose higher than 15 mg once daily is prescribed. Though concentrations were proportional to the dose, the body weight was not found to be a determining factor for dose adjustment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Chromatography of benzodiazepines.

An overview of methods for the determination of benzodiazepines in biological media, based on the application of chromatographic techniques, is presented. A general discussion of the techniques in terms of stability, selectivity, validation, standardization, detection and sensitivity is given. No single technique can be claimed as the method of choice for benzodiazepines. Gas chromatography with electron-capture detection has some strong claims and shows generally good sensitivity and reproducibility. High-performance liquid chromatographic equipment is readily available in most laboratories. The ultimate choice of an assay method for benzodiazepines will be determined by the clinical application (routine monitoring, pharmacokinetics, overdose, forensic medicine) and by the characteristics of the benzodiazepine, the expertise of the analyst, the equipment available, the desired sensitivity and specificity and the time involved in method development or adaptation and validation.

Anti-Anxiety Agents↗
PubMed1990

Influence of exercise on nitroglycerin plasma concentrations after transdermal application.

Nitroglycerin plasma concentrations following transdermal application were measured in nine healthy subjects during supine rest position or during supine rest interrupted by sitting or exercising for 20 min. Sitting led to almost doubling of the average plasma concentrations (0.31 ng ml-1 before sitting, 0.55 ng ml-1 at the end of the sitting period), but exercise was accompanied by a much more marked increase in average plasma concentrations, which reached its maximum 5 min after ending exercise (0.22 ng ml-1 before exercise, 1.26 ng ml-1 5 min after the exercise period). Changes of bioavailability as well as of systemic clearance might be involved in the exercise-induced increase in plasma nitroglycerin concentrations.

Administration, Cutaneous↗
PubMed1990

Pharmacokinetics of CGP 6140 (amocarzine) after oral administration of single 100-1600 mg doses to patients with onchocerciasis.

The concentrations of CGP 6140 [4-nitro-4'-(N-methyl-piperazinylthiocarbonylamido)-diphenylamine] and of its N-oxide metabolite, CGP 13,231, were measured in plasma and urine after single oral dose of 100-1600 mg of CGP 6140 to 41 fasted Ghanaian patients with Onchocerca volvulus infections. The absorption of CGP 6140 was rapid and its terminal elimination half-life was about 3 h. The plasma concentrations of CGP 6140 were essentially proportional to the dose. A greater variability in plasma concentrations was apparent after the 800 and 1600 mg doses indicating a poor bioavailability of the drug administered in fasting conditions to several patients. In plasma, the concentrations of CGP 13,231 were similar to those of CGP 6140. The amount of CGP 13,231 excreted in urine was 25-40% of the dose of CGP 6140 whereas only 1.5% was excreted as unchanged drug. If a single dose of drug is used for the treatment, the plasma concentration would be maintained for 3-4 h at a high level. At 8 h, the concentration falls to about 10% of the Cmax. If sustained plasma concentrations of the drug are needed for efficacy, twice daily administration would maintain the minimum concentration at about 10% of the Cmax.

Chromatography, High Pressure Liquid↗
PubMed1990

The influence of food on the pharmacokinetics of CGP 6140 (amocarzine) after oral administration of a 1200 mg single dose to patients with onchocerciasis.

Eleven male patients from Mali with Onchocerca volvulus infections received in random order a 1200 mg single oral dose of CGP 6140 after an overnight fast and after food intake. The concentrations of CGP 6140 and of its N-oxide metabolite, CGP 13231, were measured in plasma and urine. Mean (+/- s.d.) AUC CGP 6140 values were 67.0 +/- 10.8 mumol l-1 h in fed and 22.0 +/- 17.2 mumol l-1 h in fasting patients. The mean maximum concentrations (Cmax) in plasma +/- s.d. were 12.7 +/- 2.8 mumol l-1 in fed and 4.7 +/- 4.1 mumol l-1 in fasting patients. The median time to Cmax was 3 h in fed and 2 h in fasting patients. Mean (+/- s.d.) AUC of the N-oxide metabolite was 59.9 +/- 10.7 mumol l-1 h in fed and 23.4 +/- 16.2 mumol l-1 h in fasting patients. The urinary recovery was less than 0.5% of dose for CGP 6140 in both fed and fasting conditions. It was 30.1 +/- 11.5 and 11.4 +/- 8.0% of the dose for the N-oxide metabolite in fed and fasting conditions, respectively. Variability in plasma concentrations and urinary recovery of CGP 6140 and of the N-oxide metabolite was greater in fasted patients. The low solubility of CGP 6140 in aqueous solutions at neutral pH and its higher solubility at acidic pH might explain the increase in bioavailability after food intake. The administration of CGP 6140 after food intake is therefore recommended for an optimal systemic effect.

Administration, Oral↗
PubMed1989

Determination of oxiracetam in plasma and urine by column-switching high-performance liquid chromatography.

A column-switching high-performance liquid chromatographic method was developed for the determination of oxiracetam in plasma and urine. A sample of plasma (250 microliters) or urine (10 microliters) is mixed with the internal standard solution, 4.2 ml of acetonitrile-water (1000:4, v/v) and 0.8 ml of dichloromethane, and 1 ml of the clear solution is injected onto a first column filled with Li-Chrosorb NH2. The sample is eluted with acetonitrile-water (95:5, v/v). The portion of the eluate (heart-cutting) from this column containing the compounds of interest is selected and loaded on a Nucleosil NH2 column and eluted with acetonitrile-water (90:10, v/v). During this chromatography the first column (LiChrosorb NH2) is rinsed with acetonitrile-water (50:50, v/v). Ultraviolet detection at 200 nm is used for quantitation. The limit of quantitation of oxiracetam is ca. 1.5 microM (240 ng/ml) in plasma and 76 microM (12 micrograms/ml) in urine. Oxiracetam was stable in plasma and urine samples kept frozen at -20 degrees C for nine months and one year, respectively.

Chemical Phenomena↗
PubMed1989

High-performance liquid chromatographic determination of pirprofen and five of its metabolites in human plasma without hydrolysis and in human urine before and after chemical hydrolysis.

Selective high-performance liquid chromatographic methods for the simultaneous determination of pirprofen and five of its metabolites either in plasma or in urine before and after chemical hydrolysis were developed. After addition of an internal standard and a buffer, the compounds were extracted from plasma using reversed-phase C18 Bond-Elut columns and from urine using pre-packed silica Extrelut 1 columns, back-extraction into sodium hydroxide and acidification of the alkaline phase before injection. Pirprofen, its five metabolites and the internal standard were separated using a linear elution gradient chromatographic system and wavelength programming. The analysis of spiked samples demonstrated the good accuracy and precision of the methods with limits of quantitation of 100 or 200 ng/ml for the different compounds in plasma, 200 or 360 ng/ml in urine without hydrolysis and 1 or 1.8 micrograms/ml in urine after chemical hydrolysis.

Chemical Phenomena↗
PubMed1989

Determination of xylometazoline in plasma and urine by gas chromatography using a fused-silica capillary column and an electron-capture detector.

A sensitive method is described for the determination of unchanged xylometazoline in plasma and urine at concentrations down to 35 nmol/l. After addition of naphazoline as an internal standard, both compounds are extracted with dichloromethane-diethyl ether (20:80) at pH 10, back-extracted with an acidic solution and re-extracted from a sodium hydroxide solution with dichloromethane-diethyl ether (20:80). The compounds are then derivatized with heptafluorobutyric anhydride in the presence of pyridine. The derivatives are determined by capillary gas chromatography using electron-capture detection.

Chemical Phenomena↗
PubMed1989

Evaluation of the gastric absorption and emptying of drugs under various pH conditions using a simple intubation method: application to diclofenac.

Sodium diclofenac (50 mg) together with [14 C]-PEG as a non-absorbable marker were dissolved in 400 ml of water (A), phosphate buffer pH 7.5 (B) or a homogenized meal (C). Each of these was ingested in random order by six volunteers on 3 consecutive days. Some gastric absorption of the drug was established with C but the plasma drug concentration-time profiles mainly reflected the process of gastric emptying.

Absorption↗
PubMed1989

High performance liquid chromatographic determination of nicotine and cotinine in plasma and nicotine and cotinine, simultaneously, in urine.

Three analytical procedures were developed to determine nicotine in plasma, cotinine in plasma and, simultaneously, nicotine and cotinine in urine. After liquid or solid-phase extraction, the purified aqueous phase is injected into a high performance liquid chromatograph equipped with an ultra-violet detector using a CN Spheri-5 micron cartridge-column with an inner diameter of 4.6 mm and a length of 10 or 22 cm. The limit of quantitation for nicotine in plasma was around 8 to 15 ng/ml, that of cotinine in plasma around 50 ng/ml and that of nicotine and cotinine in urine around 170 ng/ml and 70 ng/ml, respectively. The limit of detection of nicotine in plasma was around 1 ng/ml and that of nicotine and cotinine in urine around 20 ng/ml and 10 ng/ml, respectively. The passive exposure to cigarette smoke by non-smokers and the "resting levels" of nicotine in plasma and urine of smokers were studied. The analytical methods were set up to study the pharmacokinetics and bioavailability of nicotine in healthy volunteers following single and repeated administrations of different doses of transdermal nicotine systems.

Amphetamine↗
PubMed1989

Pharmacokinetics and bioavailability of nicotine in healthy volunteers following single and repeated administration of different doses of transdermal nicotine systems.

Healthy nicotine-dependent smokers were applied different doses of transdermal nicotine systems (TNS) during single and repeated administrations. Plasma and urine nicotine and cotinine concentrations were determined by high performance liquid chromatography (HPLC). After single application of TNS, the maximal concentration (Cmax) and area under curve (AUC) of nicotine in plasma as well as the amount of nicotine excreted in urine were linearly related to the dose. The stable urinary cotinine excretion was not influenced by the amount of nicotine delivered by the TNS. The relevant 24 h plasma nicotine concentration reached after TNS application compares well with the plasma nicotine footpoints--not the peaks--observed in moderate to heavy cigarette smokers. A comparison between different nicotine doses from different TNS allowed to conclude to the functionality of the systems as regards pharmacokinetics and bioavailability. One or two hours after removal of the systems, there was a very slow decline of the nicotine concentrations. After repeated application of TNS, there was evidence for only a very limited nicotine accumulation in plasma (+14%) or in urine (+9%) over 10 days. The steady-state of nicotine was reached within 4 days. The continuous delivery of nicotine over 24 h resulted in an early morning plasma concentration which probably decreases or prevents the craving for the first cigarette.

Administration, Cutaneous↗
PubMed1988

Fully automated analytical system using liquid-solid extraction and liquid chromatography for the determination of CGP 6140 in plasma.

Liquid-solid extraction on disposable extraction columns (DECs) and liquid chromatography can be combined in a completely automated analyser. The Gilson ASPEC system was used to develop a procedure for the determination of CGP 6140 in plasma. Both sample preparation via C8 Bond-Elut DECs and injection were fully automatic. The fully automated system prepared the samples by performing the same operations as for a manual procedure. The DEC was first wetted with methanol, then with water. A 400-microliters volume of plasma and 40 microliters of the internal standard solution, diluted with 1 ml of water, were applied to the DEC, rinsed with 10(-2) mol/l dipotassium hydrogenphosphate and eluted from the DEC with 300 microliters of acetonitrile-methanol (50:50, v/v). The eluting strength of the eluate was reduced by dispensing 1 ml of water into each vial prior to direct injection into a Spherisorb ODS column via a 1-ml loop. This allowed the reconcentration of the extracted compounds on the top of the column, as they were injected in a large volume of solvent of lower eluting strength than the mobile phase [acetonitrile-methanol-4 x 10(-3) mol/l ammonia solution (54.5:5:40.5, v/v/v)]. Reproducibility results are presented.

Chemical Phenomena↗
PubMed1988

Determination of the S(+)- and R(-)-enantiomers of baclofen in plasma and urine by gas chromatography using a chiral fused-silica capillary column and an electron-capture detector.

A sensitive and enantiospecific gas chromatographic method for the determination of the S(+)- and R(-)-enantiomers of baclofen (I and II) in plasma and urine has been developed and validated. The method is based on the complete resolution of the derivatized enantiomers on a chiral fused-silica capillary column. The hydrochloride salt of a (-)-fluoro analogue of baclofen (III.HCl) was used as the internal standard in plasma, the hydrochloride salt of a (+)-fluoro analogue of baclofen (IV.HCl) as the internal standard in urine. Rapid and convenient isolation of the compounds was achieved using reversed-phase Bond-Elut C18 columns. After elution, the compounds were converted into isobutyl esters and purified by base-specific solvent extraction. The isobutyl esters were then N-acylated with heptafluorobutyric anhydride. The derivatives were quantitated after separation on the chiral column using electron-capture detection. The analysis of spiked plasma and urine samples demonstrated the good accuracy and precision of the method, with limits of quantitation of 25 nmol/l for I and II in plasma and of 2 mumol/l for I and II in urine. The method appears to be suitable for use in pharmacokinetic studies of the enantiomers in plasma and urine from animals and man after administration of the racemic baclofen.

Acylation↗