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Biomedical subjects

G Nicot

Publications and source records attributed to G Nicot.

At least 19 recordsLinked to original sources
PubMed1992

Pharmacokinetics of vinorelbine in man.

The pharmacokinetics of vinorelbine has been investigated by a new HPLC method in 8 cancer patients receiving 8 weekly doses (30 mg.m-2) administered by brief infusion (15 min). The plasma concentration-time curves showed a tri-exponential decay with a long terminal half-life (44.7 h) and a high volume of distribution (Vz = 75.61.kg-1). The concentrations after the 8th infusion were significantly lower than after the 1st infusion, but without significant modification of CL (1.28 l.h-1.kg-1) or AUC (0.80 mg.l-1.h). The pharmacokinetic parameters exhibited wide interindividual variations. The results are consistent with those of previous RIA studies, although the HPLC method appears to be more specific and more precise.

Aged↗
PubMed1990

Tianeptine and its main metabolite. Disposition in chronic renal failure and haemodialysis.

The disposition of the antidepressant tianeptine and its MC5 metabolite (pentanoic acid analogue of tianeptine) was studied following a single 12.5 mg oral dose of tianeptine sodium salt in 20 patients with chronic renal failure. In 12 patients (group I) having a creatinine clearance of less than 19 ml.min-1 the pharmacokinetics parameters for tianeptine and MC5 metabolite were determined and compared with those obtained in a matched control group (group II). The other 8 patients (group III) were functionally anephric and were studied during 1 dialysis to assess the haemodialysis clearances of tianeptine and MC5 metabolite. The comparison between groups I and II showed that renal failure did not appear to affect the disposition of parent tianeptine. However, the MC5 metabolite terminal half-life was found to be increased in renal patients compared to controls (14.2 +/- 9.3 h vs 4.9 +/- 1.7 h). Due to a large interindividual variability the difference did not reach a significant level (P = 0.054). According to the antidepressant activity of the MC5 metabolite in pharmacological tests, the sustained rise in its plasma level suggests that a reduced daily dose should be administered and 12.5 mg of tianeptine should be given twice daily to patients with chronic renal failure. In patients from group III elimination of the compounds by haemodialysis was found to be low. The dialysis clearances were 3.9 +/- 9.9 ml.min-1 and 19.2 +/- 8.6 ml.min-1 for tianeptine and its MC5 metabolite respectively. This low dialysability has 2 clinical implications. Firstly, patients currently undergoing haemodialysis and treated by tianeptine could be given the drug without taking dialysis into account. Secondly, haemodialysis does not appear to be an effective method for tianeptine elimination in cases of overdosage.

Administration, Oral↗
PubMed1989

Pharmacokinetics of amineptine after single-dose, repeated treatment and study of the at-risk populations.

In this paper, three different studies are discussed. First, pharmacokinetics of the tricyclic antidepressant amineptine (Survector) and its main metabolite were investigated in young healthy adults. Amineptine was rapidly absorbed. Mean peak plasma concentrations of amineptine and its metabolite occurred 1 and 1.5 h, respectively, after drug administration. The mean apparent volume of distribution was large: 2.4 L/kg. Elimination was rapid. T 1/2 (half-life) was 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). In a second study in young patients, no change in pharmacokinetic parameters was observed after a 10-day course of repeated treatment with the drug. Finally, pharmacokinetics of amineptine and its main metabolite were studied in elderly patients on day 1 and after a repeated administration for 15 days. There was no significant age-linked change in the pharmacokinetics of amineptine even if half-life and area under the curve of the metabolite were all greater in the elderly subjects than in young adults. Pharmacokinetic parameters of amineptine and its metabolite were not affected by repeated administration over 15 days. The pharmacokinetic characteristics of amineptine in elderly subjects do not necessitate any dosage alteration for this population.

Adult↗
PubMed1989

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↗
PubMed1989

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↗
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↗
PubMed1989

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↗
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↗
PubMed1986

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↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1983

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↗
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↗