The distribution of VPA has been investigated in several brain areas of the rat, and GABA increases were measured. A biphasic exponential decay was observed for VPA; the slowest decrease was noted in the olfactory bulbs and in the hypothalamus where GAD and GABA-T activities were the highest. The data may be correlated with the prolonged effect of VPA in these areas.

Animals↗

PubMedDate not supplied

Effect of the hour of administration on the pharmacokinetics of lidocaine in the rat.

The aim of the present study was to investigate an eventual influence of the hour of administration on lidocaine kinetics in the rat. 280 Wistar AF-SPF adult male rats were used for this study and maintained under controlled environmental conditions (LD: 06.00-18.00) during the month of October. A single 50 mg X kg-1 dose of lidocaine was given by intramuscular route, at four different fixed time points of a 24 hour period (i.e.: 10.00, 16.00, 22.00 and 04.00) to 70 rats. Blood samples were taken at the following time points: 5, 15, 30 min., 1, 2, 4 and 6 hours after the drug administration. Lidocaine plasma levels (free and bound) were determinated according to a specific gas chromatographic method. The data showed circadian variations of pharmacokinetic parameters:--Elimination half-life: max. 2.12 +/- 0.05 h at 10.00, min. 1.50 +/- 0.03 h at 16. --Initial concentration: max. 5.05 +/- 0.65 micrograms X ml-1 at 16.00; min. 2.97 +/- 0.29 micrograms X ml-1 at 04.00.--Elimination constant rate: max. 0.4618 +/- 0.0094 h-1 at 16.00, min 0.3279 +/- 0.0079 h-1 at 10.00.--Area under curve (experimental): max. 11.11 +/- 1.07 micrograms X kg-1 X h-1 at 16.00, min. 7.45 +/- 0.84 micrograms X kg-1 X h-1 at 04.00.--Apparent volume of distribution: max. 16.67 +/- 1,67 L X kg-1 at 04.00, min. 9.75 +/- 1.04 L X kg-1 at 16.00. The lidocaine-free fraction varied with time and the protein binding of lidocaine showed a circadian variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

PubMedDate not supplied

Diazepam: kinetic profiles in various brain areas, plasma and erythrocytes after chronic administration in the rat.

The regional distribution of diazepam (DZP) was established in eleven discrete brain areas in the rat after i.m. chronic treatment (15 days; 5 mg/kg/day). In addition, the kinetic profiles of this drug were investigated in plasma, eryhtrocytes, and three CNS regions (nucleus caudatus, hippocampus, and cerebellum) upon which the pharmacokinetic study was focused. The modifications occuring in plasma-protein binding and erythrocytes binding were reported. In the CNS, the DZP was rapidly distributed; its concentrations and its kinetic profiles were not uniform in the different brain areas studied. The highest amount of DZP was noted in the hypothalamus, while nucleus caudatus and colliculi also presented important DZP levels. Concerning the kinetic parameters after chronic administration, an increase in the elimination half-life time value in central and peripheral compartments, as compared to values reported after acute administration, was observed. The study of cerebral DZP levels as compared with those in the erythrocytes or in plasma suggests a linear correlation in the three CNS areas investigated. These experimental results demonstrate the interest of such studies for psychotropic drug monitoring.

Animals↗

PubMedDate not supplied

Effects of sodium valproate on diazepam: kinetic profiles in plasma, erythrocytes, and different brain areas in the rat.

The kinetic profiles of diazepam (DZP) were investigated in plasma, erythrocytes, and discrete brain areas in the rat, and the effects of valproic acid (VPA), given as sodium valproate, on kinetic parameters were analyzed. The experiments were performed on two groups of rats treated daily for 15 days, the first receiving only DZP (5 mg/kg/day i.m.), the second treated with DZP (5 mg/kg/day i.m.) and VPA (200 mg/kg/day i.p.). Our results indicate that VPA influences the plasma-protein binding and erythrocyte levels of DZP, as well as its kinetic profile. These data are discussed with regard to the modifications observed in the different brain areas (cerebellum, hippocampus, whole cortex, and pons-medulla) during administration of VPA and DZP. The results presented in this study offer evidence that VPA exerts a peculiar action on the "impregnation" and kinetics of DZP in the CNS, and therefore these findings may be of importance in clinical pharmacology and treatment of epilepsies.

Animals↗

PubMedDate not supplied

[Plasma MHPG, peripheral noradrenergic marker and hormonal plasma levels of cortisol-T3-T4-TSH in depressive syndromes].

Based on the hypocatecholaminergic hypothesis in the depressive syndromes, this survey on 30 depressed patients compared to 21 control patients, attempts to state exactly the potential interactions between the noradrenergic system and the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid neuroendocrine axis. The biological indices used during this survey are: total plasmatic MHPG, the basic plasmatic cortisol, the thyroid hormones T3, T4, free T4, and the TSH. The results of this survey reveal a significative increase of the basic plasmatic cortisol among the depressed patients, including dysthymics, a decrease of the plasmatic MHPG during major depressions, and a significant fall of the total T3 among depressed men, as well as some correlations between the different axes, the interpretation of which remains "ticklish".

Adult↗

PubMedDate not supplied

[Quantitative value of the diagnostic test for a respiratory allergy: phadiatop].

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Humans↗

PubMedDate not supplied

[Glutathione peroxidase deficiency in patients in chronic coma treated by prolonged enteral alimentation].

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Adult↗

PubMedDate not supplied

[Use of calcium inhibitors in neuropsychiatric pathology].

The use of calcium channel blockers is usual in cardiology today, but seem to spread to others specialties, particularly in the field of neuropsychiatry. The authors report the major clinical studies in neurology (treatment of migraines, epilepsia, dizziness and ischemic stroke) where flunarizine and nimodipine seem to have an important role. In psychiatry, their introduction is more recent. However, some encouraging results have been noted in the treatment of panic disorder, Gilles de la Tourette disease and mania.

Brain Diseases↗