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Biomedical subjects

G Lachatre

Publications and source records attributed to G Lachatre.

34 records · Page 2Linked to original sources

Simultaneous plasma determination of floctafenin and its major metabolites by high-performance liquid chromatography: preliminary observations in children.

An isocratic reversed-phase ion-pair liquid chromatography with UV detection at 350 nm for the determination in human plasma of floctafenin (F) and its three main metabolites--floctafenic acid (FA), hydroxyfloctafenin (HOF), and hydroxyfloctafenic acid (HOFA)--is reported. Analytes and internal standard were extracted from acid plasma into ethyl acetate, and this organic phase was evaporated to dryness. This extraction yielded plasma drug recoveries of greater than 72%. Using 1 ml of plasma, the lower quantification limit was 0.05 microgram ml-1 with excellent linearity up to 0.8 microgram ml-1 for HOF and HOFA and up to 4.0 micrograms ml-1 for F and FA. The reproducibility and the selectivity of the method for several drugs thought likely to be administered in conjunction with F, were demonstrated. This method has been successfully applied to a pharmacokinetic study with a single 10 mg kg-1 oral dose in ten children.

Child↗

Single-dose pharmacokinetics of amineptine and of its main metabolite in healthy young adults.

The pharmacokinetics of the tricyclic antidepressant amineptine (Survector) and its main metabolite were studied in 12 young healthy adults (6 men, 6 women; mean age 35.8 yr). Plasma samples were taken over 24 h following a single oral dose of 100 mg amineptine chloryhdrate. Plasma levels of both compounds were determined by means of high performance liquid chromatography. Amineptine was rapidly absorbed. Mean peak plasma concentrations of amineptine and its metabolite occurred 1 h and 1.5 h, respectively, after product administration. The mean apparent volume of distribution was large: 2.4 l.kg-1. Elimination was rapid; the mean half-lives of the 2 compounds were short: 0.8 h for amineptine and 2.5 h for the metabolite. The mean apparent plasma clearance of amineptine was high (124.8 l.h-1). When the results were adjusted for body weight and surface area, no significant difference in pharmacokinetic parameters was found between men and women. Given its pharmacokinetic characteristics there is no risk of amineptine accumulation and thus it is a particularly easy drug to manage. A standard dosage of amineptine was defined for use in healthy young adults.

Adult↗

Theophylline toxicity risks and chronic renal failure.

Serum theophylline and metabolites (methyluric acids, mono- and dimethyl xanthines) concentrations from uremic patients, either with end-stage renal failure or on peritoneal dialysis or maintenance hemodialysis, were investigated by HPLC and compared with those obtained in non-uremic subjects. We conclude that in uremic patients serum theophylline metabolites, particularly serum 1,3-dimethyluric acid, are significantly higher than in non-uremic subjects even when serum theophylline is lower. A slight increase in the free fractions of serum theophylline was also observed in these patients. All these findings could explain the toxicity signs noted in some patients with chronic renal failure and treated with very low doses of theophylline.

Adult↗

Ion-pair extraction and high-performance liquid chromatographic determination of tianeptine and its metabolites in human plasma, urine and tissues.

An isocratic reversed-phase ion-pair liquid chromatographic method for the determination of tianeptine and its two main metabolites in plasma, urine and tissues, using an internal standard, is reported. The influence of two stationary phases on the retention of the drugs was studied. The drugs were extracted as ion pairs, using a heptane-octanol-tetraheptylammonium bromide mixture (98:2:0.5, v/v/w) as extraction solvent. This extraction procedure yielded plasma drug recoveries of greater than 60% and allowed UV detection at 220 nm without interference from endogenous components of plasma, urine or tissues. Linear standard curves up to 1.00 micrograms/ml and drug determination down to 0.01 microgram/ml were observed. This method has been successfully applied to the analysis of human plasma and urine samples and of encephales from tianeptine-dosed rats.

Animals↗

High-performance liquid chromatographic method for the determination of amineptine and its main metabolite in human plasma.

An isocratic reversed-phase ion-pair liquid chromatographic method for the determination of amineptine and its main metabolite in plasma using an internal standard, is reported. The effects of stationary phase alkyl chain length and the concentration of alkyl sulfonate in the mobile phase were investigated. The drugs were extracted as ion pairs and the influence of various parameters on the extraction efficiency are discussed. Using a heptane-octanol-tetraheptylammonium bromide mixture (98:2:0.5, v/v/w) as extraction solvent, more than 60% of each drug was recovered with a very good selectivity. UV detection at 220 nm allowed drug determination down to 0.010 microgram/ml. Linear standard curves up to 1.00 microgram/ml were observed.

Biotransformation↗

Characterization of the esterases of the mitochondrial fraction of guinea pig cortical renal cells.

The esterase activity of the mitochondrial fraction from cortical renal cells was studied in guinea pigs aged 15, 21, 30, and 120 days. The rate of hydrolysis of beta-naphthyl acetate was measured by incubating aliquots of mitochondrial preparations with physostigmine, diisopropylfluorophosphate, HgCl2, and p-hydroxymercuribenzoate. Enzyme activity was mainly due to the heterogeneous aliesterase group: some aliesterases were sensitive to physostigmine, others to organophosphorus compounds and/or to HgCl2; a C-esterase stimulated by organomercurials and similar to that described by Bergmann et al. in hog kidney was detected (F Bergmann, R Segal, S Rimon. Biochem J 67:481-486, 1957); arylesterase activity was very weak. Acetylthiocholine used as substrate showed there was no cholinesterase activity in the mitochondrial fraction.

Aging↗

High-performance liquid chromatographic method for the determination of bamifylline and its three metabolites in human plasma.

The performance of a gradient elution normal-phase system and of two isocratic elution reversed-phase ion-pair systems was investigated for the high-performance liquid chromatographic separation of bamifylline and its three metabolites. Three packings and mobile phases were tested and the best separation was achieved using a reversed-phase ion-pair system with Hypersil ODS 3 micron as stationary phase. The effects of alkyl chain length and concentration of alkyl sulfonates, salt concentration, column temperature and competing amine on separation and peak tailing are discussed. The determination of bamifylline and metabolites in human plasma using the defined optimal chromatographic conditions is reported.

Chromatography, High Pressure Liquid↗

[Phosphonate esterase activity in human serum (author's transl)].

A simple methodology for the spectrophotometric assay of phosphonate esterase activity in human serum samples is described, featuring incubation at 30 degrees C in a medium containing p-nitrophenol and phenyl-phosphonic acid ester. Reproducibility of the method as well a mean values in normal patients vs age and sex are reported. Serum activity appears to be increased almost exclusively during pregnancy or administration of estrogenic drugs (as oral contraceptives or in prostate neoplasms).

Female↗