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Biomedical subjects

G Lachâtre

Publications and source records attributed to G Lachâtre.

48 records · Page 3Linked to original sources
PubMed1995

Population pharmacokinetics of amikacin in intensive care unit patients studied by NPEM algorithm.

The population pharmacokinetics of amikacin was studied in 40 intensive care unit patients (212 plasma concentrations) by NPEM algorithm using a one-compartment model. The population was best characterized by the following pharmacokinetic parameters: renal clearance relative to creatinine clearance (Cs = 0.96 +/- 0.33), and either the total volume of distribution (Vd = 23.9 +/- 7.0 l) or the volume of distribution relative to body weight (Vs = 0.36 +/- 0.10 l.kg-1. The volume of distribution was increased with respect to the usual value of 0.25 l.kg-1. The statistical distribution of these pharmacokinetic parameters was approximately gaussian, with no significant correlation between volume of distribution and clearance. The medians and standard deviations of Cs and Vs were used as reference population values to estimate the pharmacokinetics of amikacin in a second group of 29 patients by the bayesian method, with two blood samples per patient. For each patient, the fitted parameters were able to predict the plasma concentrations of amikacin during the next 72 h with no significant bias and good precision (2.9 mg.l-1 for peaks and 0.5 mg.l-1 for troughs). This study confirms the ability of the NPEM algorithm to provide reference population values for use in bayesian monitoring of aminoglycoside therapy.

Adolescent↗
PubMed1995

Trypanosoma brucei brucei: antitrypanosomal evaluation of stilbamidinium hexachloroiridiate on the murine CNS model and iridium serum kinetics in infected sheep.

Stilbamidinium hexachloroiridiate was found trypanocidal in vitro against Trypanosoma brucei brucei IPP at 600 microM after a 1 h incubation period and 30 microM after 24 h. This activity was confirmed in mice with a subcutaneous treatment at 20 mg/kg in a single dose. It was then evaluated on T.b. brucei murine CNS model. At the early stage, a subcutaneous treatment at 2 mg/kg/day x 5 cured 50% mice where-as one single dose at 10 mg/kg was completely inactive. Higher doses failed to cure the mice. Nevertheless, hexachloroiridiate salt of stilbamidine was 3.3 fold less toxic than dihydrochloride salt. Although the compound appeared inactive at the late stage of the murine trypanosomiasis, the difference of toxicity justified its evaluation on the early stage of sheep trypanosomiasis. The compound was trypanocidal at 2 mg/kg in a single dose when administered 8 days after infection. The study of iridium serum kinetic showed that stilbamidinium hexachloroiridiate was distributed rapidly according to a monocompartmental model. Moreover, iridium persisted in serum for a long time. The compound in aqueous suspension with 1% carboxymethylcellulose acted therefore as a controlled release system with a bioavailability allowing its trypanocidal action at the early stage.

Animals↗
PubMed1989

[Assay of biogenic amines by bioluminescence].

A bioluminescent procedure to measure noradrenaline and serotonin has been realized. The amines are oxidized by the monoamine oxidase of pig brain mitochondria. The NH3 generated in this reaction is directly measured by enzymatic reaction. The coenzyme of this last reaction is the NADH,H+ which is measured with a bioluminescent system: the FMN-oxidoreductase-luciferase. The extension to other amines is possible, it depends only of the specificity of the monoamine oxidase.

Biogenic Amines↗
PubMed1987

Rapid assay of N-acetyl-beta-D-glucosaminidase isoenzymes in urine by ion-exchange chromatography.

We describe a new method for separating and measuring urinary N-acetyl-beta-D-glucosaminidase isoenzymes by "high-performance" liquid chromatography. Isoenzymes are eluted from the anion-exchange column with a one-step linear gradient of NaCl solution. For continuous post-column quantification of the activities of these isoenzymes, we use an on-line post-column reactor and 4-methylumbelliferyl-N-acetyl-beta-D-glucosaminide as substrate; the methylumbelliferone formed in this reaction is quantified fluorimetrically. We discuss the effects of varying different components of the assay: NaCl concentration, the pH of the mobile phase and of the reaction reagent, substrate concentration, incubation temperature, and the geometry of the post-column reactor.

Acetylglucosaminidase↗
PubMed1982

Gentamicin and sisomicin - induced renal tubular damage.

Early signs of aminoglycoside - induced renal tubular damage were detected in 26 patients given gentamicin and 23 given sisomicin. The urinary elimination of 3 low molecular weight proteins (LMWP) - beta 2 microglobulin, retinol binding protein and lysozyme (LZM), and the urinary activity of 2 enzymes - alanine aminopeptidase and N-acetyl-beta-glucosaminidase - was measured before, during and after treatment. In gentamicin - treated patients LMWP elimination increased, especially LZM which rose markedly during treatment and returned to normal values after its end. Enzyme activities also rose while gentamicin was being given. Sisomicin produced smaller changes. As neither the mean serum creatinine nor the mean urinary elimination of transferrin were increased, glomerular function was probably not affected. However, tubular damage was detected, as shown by the LMWP output (especially LZM) and increased enzyme activity. Urinary LMWP and enzyme measurements are presented as sensitive and reliable methods to monitor early aminoglycoside - induced tubular impairment. It is suggested that the different renal toxicities of gentamicin and sisomicin are related to differences in their accumulation in the renal cortex.

Acetylglucosaminidase↗
PubMedDate not supplied

Analytical findings in a suicide involving sodium azide.

A 47-year-old laboratory assistant ingested approximately 9 g of sodium azide powder and died 4 h later at a hospital. A high-performance liquid chromatographic method using diode-array detection has been developed for the determination of an azide benzoyl derivative in blood (after a simple deproteinization) and in several tissues (after homogenization in a neutral buffer and deproteinization of the supernatant). The blood concentration in this case was lower than those previously published. The highest azide concentration was found in lung tissue. A complete toxicological screening revealed the presence of cyanide in blood, which has been previously reported twice, but for the first time, it was confirmed by mass spectrometry. Whether the production of cyanide in the presence of azide took place in vivo or postmortem remains unknown; the nature of the metabolic pathway involved also remains unknown.

Azides↗
PubMedDate not supplied

A screening procedure for the determination of 13 oral anticoagulants and rodenticides.

A technique for the simultaneous identification and quantitation of 13 hydroxycoumarin and indandione anticoagulant drugs and rodenticides from human serum by reversed-phase liquid chromatography with diode-array detection has been developed. High-performance liquid chromatography was performed using gradient elution with an acetonitrile and phosphate buffer on a Nucleosil ODS column. Ultraviolet spectra from 200 to 400 nm were recorded on-line during the analysis and compared with spectra stored in a library. For the spiked 2 mL of serum, acidic and alkaline liquid-liquid double extraction with diethylether-ether acetate (50:50, v/v) was conducted, and recoveries greater than 60% for most compounds were found. The detection limit was approximately 25 or 50 ng/mL for all components except for difethialone and fluindione, for which it was approximately 100 ng/mL. The standard calibration curves were linear from the detection limit to 5000 ng/mL. The within-run precision coefficient of variation (CV) was less than 10%, and the between-run precision CV was less than 20%.

Administration, Oral↗
PubMedDate not supplied

Applications of liquid chromatography--mass spectrometry in analytical toxicology: a review.

Liquid chromatography-mass spectrometry (LC-MS), after long-term development that has introduced seven major interfacing techniques, is finally suitable for application in the field of analytical toxicology. Various compound classes can be analyzed, and sensitivities for more or less polar analytes that are as good as or better than those of gas chromatography-mass spectrometry can be obtained with modern interfaces. In addition, because ionization is often softer than classical electron impact, some LC-MS interfaces are able to handle fragile species that are otherwise not amenable to MS. This review is intended to present LC-MS to less familiarized readers and to give an extensive overview of the application of the different coupling techniques to doping agents, drugs of abuse, forensic analysis, toxic compounds of various nature, and several toxicologically relevant therapeutic drugs. Experimental parameters such as the interfaces used, ionization methods, detection limits, and experimental details for exemplary applications are given.

Animals↗
PubMedDate not supplied

Determination of buprenorphine and norbuprenorphine in whole blood by liquid chromatography-mass spectrometry.

A sensitive and highly specific method for the determination of buprenorphine and norbuprenorphine in postmortem and hemolyzed whole blood using combined liquid chromatography and mass spectrometry (LC-MS) with electrospray ionization was developed. After enzymatic hydrolysis and deproteinization with acetonitrile, Extrelut-3 cartridges were used for a preliminary basic sample cleanup. Elution by toluene-ether (50:50, v/v) was followed by an acid wash with 0.05M H3PO4 and a basic re-extraction into ether. A Nucleosil C18 (150 x 1-mm i.d.) reversed-phase column was used for the chromatographic separation together with a mixture of 2mM ammonium formate buffer (pH 3) and acetonitrile (55:45, v/v) as the mobile phase. Recoveries were between 56 and 60%, and detection limits were 0.05 ng/mL for both analytes. The coefficient of variation for repeatability was lower than 4%. Limits of quantitation were 0.1 ng/mL for buprenorphine and norbuprenorphine. Reproducibility was good, and linearity was excellent in the range of 0.1 to 100 ng/mL (r > 0.9999, n = 7).

Adult↗
PubMedDate not supplied

A general unknown screening procedure for drugs and toxic compounds in serum using liquid chromatography-electrospray-single quadrupole mass spectrometry.

A complete general unknown screening procedure was developed using liquid chromatography-mass spectrometry (LC-MS), a coupling that can increase the range of compounds amenable to MS. Sample preparation was by solid-phase extraction on a mixed-mode support in parallel with serum deproteination in order to recover the most hydrophilic compounds. Chromatography employed a reversed-phase narrow-bore column (150 x 1-mm i.d.) and a 50-min gradient elution at low flow-rate (50 microL/min), compatible with the electrospray source used without splitting nor heating. The single quadrupole LC-MS instrument used was operated in the 100 to 1100 mu mass range in both the positive and negative modes, with two different, alternated collision-induced dissociation voltages in the source, in order to obtain the molecular or pseudo-molecular ions as well as fragments for the compounds analyzed. The addition of spectra obtained at low and high fragmentation voltages gave reconstructed spectra for each polarity, representing library entries. Finally, a program was created in order to detect the peaks of interest in the chromatographic noise using a very efficient signal processing algorithm, compute their relative retention time with respect to the internal standard (glafenine), draw their reconstructed spectra, search them in the libraries, and edit a report.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

[Rape drugs: pharmalogical and analytical aspects].

Rape drugs or compounds used for chemical submission are current hot topics of numerous media based on a few well-documented identified cases. In the aim of considering the compounds potentially involved and subsequently the samples to collect and the toxicological analyses to perform, and according to the aggressor's viewpoint (victim submission and impunity of himself or herself), the characteristics of such compounds were drawn following the drug pharmacological properties. The compounds or therapeutic classes potentially used are numerous and diverse because the expected effects can be obtained by many neuropharmacological mechanisms or combinations of mechanisms. However, a few drugs (i.e. several benzodiazepines, and gamma-hydroxybutyrate) seem to be the ideal candidates owing to advantageous pharmacological properties (low blood concentrations, short elimination half-life) and practical ones (availability, galenic forms). It appears that the quality and precocity of biological specimen collection, the use of specific and sensitive analytical techniques, and the collaboration between the clinician and the toxicologist, are the essential keys for successful toxicological investigations when a case of chemical submission is suspected.

Female↗