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Biomedical subjects

J H Trouvin

Publications and source records attributed to J H Trouvin.

At least 37 records · Page 2Linked to original sources
PubMed1991

In vivo evidence for carrier-mediated brain uptake of a new 2-amino-2-oxazoline (COR3224) via the purine transport system in rat.

We studied the brain uptake of a new 2-amino-2-oxazolamines derivative (COR3224) in the rat by means of the rapid intracarotid injection technique described by Oldendorf. The brain uptake index (BUI) of labelled COR3224 decreased progressively from 10% to 5% when concentrations of unlabelled compound were increased. The effect of various compounds indicated that COR3224 is transported into the brain by the purine carrier. The affinity of COR3224 for this carrier (Km = 5.68 microM) was higher than that of adenine.

Animals↗
PubMed1991

Determination of a new 2-amino-2-oxazoline (COR 3224) in plasma and brain tissue of the rat by high-performance liquid chromatography with electrochemical detection.

A reversed-phase (CN as stationary phase) liquid chromatographic method with electrochemical detection is described for the quantitation of COR 3224, a new 2-amino-2-oxazoline in plasma and brain tissue of the rat. Extraction was performed with dichloromethane and detection was achieved at a working electrode potential of +0.85 V versus an Ag/AgCl reference electrode. The recovery of the method is about 80 and 60% for plasma and brain, respectively. The limit of detection was less than 10 ng/ml for both plasma and brain, five times lower than that with ultraviolet detection.

Animals↗
PubMed1991

Biogenic amines and GABA in the larval and adult forms of the nematode Nippostrongylus brasiliensis.

1. Simultaneous detection (HPLC and electrochemical detection) of biological extracts of larval and adult stages of Nippostrongylus brasiliensis was performed in order to assay biogenic amines. 2. Gamma-amino-butyric acid was assayed in the same samples. 3. Tryptophan, 5-hydroxyindoleacetic acid were at the same level in adults and larvae. 4. 5-Hydroxytryptophan, serotonin, dihydroxyphenylalanine and dopamine were significantly higher in larvae in which gamma-amino-butyric acid was not detected.

Aging↗
PubMed1991

Biogenic amines in newly-ecdysed cockroaches.

1. Simultaneous quantification (HPLC and electrochemical detection) of biological extracts have shown dopamine, N-acetyl dopamine, tryptophan, 5-hydroxytryptamine, a 5-hydroxyindolacetic acid-like substance in nervous tissue and hemolymph of Blaberus craniifer and Periplaneta americana. 2. 5-Hydroxytryptophan was only detected in head and thoraco-abdominal nerve cord. 3. Octopamine, but not N-acetyl-5-HT was quantified in the hemolymph.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Effect of L-dopa loading on 5-HTP decarboxylation in rat brain areas.

The time course of 5-hydroxytryptophan (5-HTP), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in four rat brain areas (hypothalamus, hippocampus, striatum and olfactory bulbs) were investigated after treatment with L-dopa (125 mg/kg, ip) + benserazide (50 mg/kg, ip). 5-HTP levels increased as early as 0.5 h, showed maximum accumulation at 1.5 h and returned to control levels within 4 h, while 5-HT was markedly decreased in all four structures, with a maximum effect at 1.5 h (approximately -70%) in the four areas. The decrease in 5-HT was not accompanied by changes in 5-HIAA levels. In agreement with previous studies, these data demonstrate that L-dopa loading interferes with serotonin metabolism in the rat brain. However, in addition to the releasing action of newly-synthesized dopamine, the accumulation of 5-HTP and the parallel decrease in 5-HT indicate a reduction in 5-HT synthesis. This inhibition could be explained by a competitive effect of L-dopa for aromatic aminoacid decarboxylase activity.

5-Hydroxytryptophan↗
PubMed1991

Kinetics and brain uptake of COR3224, a new 2-amino-2-oxazoline, in rats.

COR3224, a new 2-amino2 oxazoline derivative, shows antidepressant activity in the rat. This study was designed to analyse the influence of dose ranging on the brain/plasma concentration ratio of this drug. Adult male rats (250-300gr, Sprague Dawley) were given orally 10, 40 and 160 mg/Kg radiolabelled 14C-COR3224 (30 microCi/kg) in aqueous solution and were sacrificed at 0.25; 0.5; 0.75; 1; 2; 4; 6; 8; 12; 16; 24; and 30 hours post dose (5 rats per time). Plasma and brain samples were analysed for total radioactivity (T.R.) by liquid scintillation and for COR3224 (U.P.) by reversed-phase liquid chromatography and electrochemical detection. A linear relationship was found between AUC and doses administered for both TR and UP plasmatic determinations. In opposite, cerebral AUC for TR and U.P were not proportional to dose, and the evolution of the brain/plasma concentration ratios showed higher values for the 10mg/kg dose than for the 40 and 160mg/kg doses.

Animals↗
PubMed1990

High-performance liquid chromatography of a new 2-amino-2-oxazoline: application to pharmacokinetic studies in dogs.

5-(1'-Phenyl-4'-piperazinomethyl)-2-amino-2-oxazoline (1; COR3224), a derivative of 2-amino-2-oxazolines with antidepressant properties in rats, was assayed in plasma by high-performance liquid chromatography. After back extraction, 1 and a ortho-O-methyl derivative of 1 as the internal standard were separated by reversed-phase liquid chromatography and measured by UV detection (235 nm). The method is rapid and specific: the detection was linear in the range 125-1000 micrograms.L-1, with a detection limit of 50 micrograms.L-1. This method allowed the determination of pharmacokinetic parameters in six beagle dogs after intravenous and oral administration of 14C-labeled 1 ([14C]1) in a crossover study. The comparison of the results obtained from total radioactivity counting and unchanged product evaluated by HPLC-UV suggest the presence of metabolites.

Administration, Oral↗
PubMed1990

Acebutolol and diacetolol plasma levels in patients undergoing myocardial revascularization with hypothermic cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) has been reported to alter the disposition of numerous drugs and consequently to modify their plasma levels. The present study was designed to delineate the time course of acebutolol (a cardioselective beta-blocker) and diacetolol (its main metabolite) plasma levels in seven patients undergoing myocardial revascularization with hypothermic CPB. All patients were given oral acebutolol twice daily until 3 hours before surgery. Initiation of CPB produced an immediate and significant, but transient, decrease in acebutolol and diacetolol plasma concentrations. Cessation of CPB was not associated with an increase in plasma beta-blocker levels. It is concluded that CPB does not induce major alterations in the time course of acebutolol and diacetolol plasma concentrations.

Acebutolol↗
PubMed1990

Nifedipine enhances amoxicillin absorption kinetics and bioavailability in humans.

Intestinal absorption of aminopenicillins in vitro uses the dipeptide carrier system. Recent experiments have reported calcium ion to be a cellular mediator of the regulation of electrolyte transport through the enterocyte membrane, especially the Na/H exchange which is partly responsible for the proton gradient energizing the carrier system. In order to assess the in vivo relevance of these data, we studied, in healthy volunteers, the influence of nifedipine, a calcium channel blocking agent, on the intestinal uptake of amoxicillin, a commonly prescribed and well-absorbed aminopenicillin. Results obtained show that 1) intestinal absorption kinetics of amoxicillin follows a zero-order process, which further substantiates the existence of a saturable carrier-mediated process for this antibiotic in humans and 2) calcium channel blockade significantly enhances both absorption rate (by 70%) and bioavailability of amoxicillin (by 21.4%) without modifying its distribution or elimination. These findings might suggest that nifedipine could enhance amoxicillin intestinal uptake by stimulating its active transport.

Adult↗
PubMed1989

Quantitation of paf-acether by release of endogenous platelet serotonin assessed by liquid chromatography with electrochemical detection.

A new method to quantitate paf-acether (paf) was developed. It is based on the measurement of serotonin released from washed rabbit platelets challenged with paf. Platelets (1 X 10(8)/ml) were exposed with or without stirring to various concentrations of paf (26-130 pM) at 37 degrees C or at room temperature. Supernatants were submitted to a 4-min liquid chromatography run and serotonin was measured by electrochemical detection. We quantitated paf from three different biological sources, human neutrophils, mouse peritoneal macrophages, and cultured mast cells, comparing a classical method, i.e., platelet aggregation with the electrochemical detection of endogenous serotonin. We found similar results since, when compared with the aggregation method, the results differed by 12 to 47%. The sensitivity of both methods was 26 pM. The between-day variation coefficient was 23 and 14% (n = 12) for the aggregation method and the serotonin release, respectively, whereas the within-day variation coefficient for serotonin quantitation was less than 5% (n = 12). The superiority of the new method lies in its simplicity, the economy of platelets, and its possibility of automation. It can be applied to any agonist or any mechanism capable of releasing serotonin from platelets and more generally when a simple and fast method for measuring serotonin is desirable.

Animals↗
PubMed1989

The systemic availability of meptazinol in man after oral and rectal doses.

We have studied the pharmacokinetics of the centrally-acting analgesic meptazinol after oral and rectal administration to 15 healthy men. Each subject took a standard 200 mg tablet orally and Witepsol H12 suppositories containing 75, 100, and 150 mg of the drug in a cross-over design. Meptazinol plasma concentrations were measured by HPLC using fluorescence detection and the pharmacokinetics determined. The tmax values for the 100 mg and 150 mg suppositories (median = 0.5 h) were statistically significantly shorter than for the tablet (median = 1.13 h), suggesting that meptazinol was more rapidly absorbed via the rectal route. Despite substantial intersubject variation in Cmax the plasma concentrations after rectal dosage were higher than after oral administration. There was a statistically significant (p less than 0.001) improvement in systemic availability for each of the suppository doses (mean approximately 15.5% compared with the oral tablet (mean approximately 4.5%).

Administration, Oral↗
PubMed1989

Effects of food intake and body weight on a serotonergic turnover index in rat hypothalamus.

Absolute levels and ratio of serotonergic compounds in food-related hypothalamic nuclei were determined with a chromatographic method comparing for control (C) versus lean (L) versus obese (O) rats. In all three groups, a second parameter, i.e., fasting (F) versus satiation (S) was superimposed on the body weight factor. Indoleamine levels failed to show statistical differences depending on the body weight and/or the nutritional status. A significant negative correlation between an index of the serotonin turnover, the 5-HIAA/5-HT ratio, and body weight was found for the paraventricular (PVN) nucleus in the C and L groups as well as for the lateral (LH) nucleus for the C and O groups. A positive correlation was found for the ventromedian (VMH) nucleus in the O group. These data suggest that the body weight factor is implicated in the central serotonergic regulation more than the feeding parameter.

Animals↗
PubMed1989

Comparison of tissular disposition of pentamidine mesylate in the rat after aerosol or parenteral administration.

The tissular distribution of pentamidine mesylate (4 mg/kg as free base) after intravenous, intramuscular, and aerosol administration in healthy rats was examined. Pentamidine levels in the plasma, lungs, liver, kidneys, and other organs were determined by high-performance liquid chromatography. Pentamidine was undetectable in the plasma after day 5. At day 1, the injected groups had high concentrations of the drug in the kidneys (32-34 micrograms/g) and spleen with much lower concentrations in the lungs and the liver (3.12-5.70 micrograms/g and 1.64-2.19 micrograms/g, respectively). Aerosol delivery of pentamidine produced negligible extrapulmonary drug levels (3.29 micrograms/g in kidneys at day 1) and high sustained pulmonary levels throughout the 60 d of the study (range 5.42-19.62 micrograms/g). The half-time of elimination was longer in the lungs and kidneys (29-45 d) than in the liver (1.4-7.0 d) regardless of the mode of administration.

Aerosols↗
PubMed1989

[Relation of the kinetics of the antisecretory effect and kinetics of blood concentration in man. Comparing cimetidine and ranitidine].

The time course of antisecretory effects of ranitidine and cimetidine and their relationship to plasma concentration were studied in 4 healthy volunteers. Placebo, cimetidine (266 mg) or ranitidine (100 mg) were infused during one hour preceding the 90 minute assessment of food-stimulated gastric acid secretion (intragastric titration); cimetidine and ranitidine blood levels and gastric acid outputs were measured at 15 min intervals. For each test a significant (p less than or equal to 0.01) correlation was found between concentration and effect. The half-life effect of ranitidine (t1/2 E) was significantly (p less than or equal to 0.05) greater than t1/2 E of cimetidine whereas their plasma half-lives (t1/2) were similar. The ratio t1/2 E/t1/2 was significantly (p less than or equal to 0.05) lower with cimetidine than with ranitidine. Explanations for this discrepancy are analyzed according to various hypotheses. The determination of t1/2 E seems to be a good approach to the duration of action of H2-antagonists. Our results show that the ratio t1/2 E/t1/2 and the t1/2 E might be important pharmacokinetic parameters to compare various H2-receptor antagonists.

Adult↗
PubMed1988

Pharmacokinetics of midazolam in anaesthetized cirrhotic patients.

The pharmacokinetics of midazolam were compared in cirrhotic patients (n = 10) and control patients (n = 9), during general anaesthesia. Total plasma clearance was 637 +/- 223 ml min-1 (mean +/- SD) in control patients and 402 +/- 170 ml min-1 in cirrhotic patients (P less than 0.05). The total volume of distribution was similar. Elimination half-life was 135 +/- 40 min in controls and 168 +/- 30 min in cirrhosis (P less than 0.05). Protein binding was evaluated by equilibrium dialysis in both groups at two concentrations of midazolam: 20 and 500 micrograms litre-1. No saturation occurred, but the free fraction was 4.9 +/- 1.7% in cirrhotic patients, compared with 1.9 +/- 0.6% in controls (P less than 0.01). Despite its mainly hepatic elimination, midazolam disposition appears to be only slightly impaired in cirrhotic patients.

Adult↗
PubMed1988

Pharmacokinetics of ofloxacin after single and multiple intravenous infusions in healthy subjects.

The pharmacokinetics of ofloxacin were investigated in eight healthy male volunteers. A single infusion (200 mg over 0.5 h) was performed on day 1, followed by a washout period of 2 weeks. Repeated administrations were performed for 4 days (200 mg every 12 h). Pharmacokinetic parameters were determined from the plasma decay curves of the single and the last of the multiple administrations. Ofloxacin kinetics after the single dose were best described by a two-phase curve with a total body clearance of 241.6 +/- 43.3 ml min-1, a volume of distribution of 112 +/- 23.1 liters, and an elimination half-life of 5.4 +/- 0.8 h. The extrapolated area under the curve (AUC0-infinity) was 14 +/- 2.3 mg.h liter-1. The pharmacokinetics were not significantly modified by repeated administration, demonstrated mainly by the AUC0-12 value of the last infusion (13.4 +/- 2.2 mg.h liter-1). We conclude that, with intravenous multiple doses every 12 h, the steady state is reached within 24 to 36 h and no abnormal accumulation or changes in pharmacokinetic parameters occur.

Adult↗
PubMed1988

Pyrazinamide and pyrazinoic acid pharmacokinetics in patients with chronic renal failure.

Pharmacokinetics of pyrazinamide and its major metabolite, pyrazinoic acid, were assessed in 10 chronic uremic patients treated by maintenance hemodialysis in comparison with 10 normal subjects. All subjects ingested a single dose of 1 g of pyrazinamide, the patients receiving the drug immediately after the end of a dialysis session. Bioavailability of pyrazinamide was only slightly increased in patients, its dialysis extraction coefficient being 55.3%. In contrast, pyrazinoic acid has an elimination rate-dependent metabolism with a bioavailability markedly increased in patients and a dialysis extraction coefficient of 59.8%. These data may lead to recommendations of a reduction in the dosage of pyrazinamide in dialysis patients. However, administering the usual dosage of the drug at the end of each dialysis session seems preferable to the daily administration of a reduced dosage.

Adult↗