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

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

[Acute toxicity of 5 intravenous anesthetics in rats depending on age and sex].

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Age Factors↗

PubMedDate not supplied

[Serum beta-glucuronidase activity in patients with epilepsy].

Little information is available on the effect produced by antiepileptic drugs on the serum beta-glucuronidase activity. According to recent findings, beta-glucuronidase serum levels are increased in patients with epilepsy just before the beginning of seizures and remain increased during several weeks; this it is suggested that determination of this enzyme could be important in the provision and the treatment of seizures. The purpose of the present study attempts to understand these changes. Our study was carried out on 49 adult healthy subjects and 48 adult epileptic patients receiving anticonvulsant therapies. Serum beta-glucuronidase activity was determined by a simplified procedure employing phenolphtalein glucuronic acid as substrate. The mean +/- SEM of serum beta-glucuronidase activity in treated patients (40.93 +/- 5.01 MSU/ml) was significantly higher than those of the healthy subjects (25.04 +/- 3.40 MSU/ml). In conclusion, the relationship between changes in serum enzyme activity, seizures and anticonvulsant therapies suggests that the determination of serum beta-glucuronidase activity presents a weak interest in predicting or treating seizures.

Adolescent↗

PubMedDate not supplied

[Apropos of the tryptophan test: technic and results obtained in 164 epileptic children].

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Child↗

PubMedDate not supplied

[Pharmacokinetic study of the regional cerebral distribution of diazepam following chronic administration. Correlations with plasma and erythrocyte levels].

The kinetic profile of diazepam (DZP) was studied in plasma, erythrocytes, and eleven discrete brain areas of the rat, after intramuscular subchronic administration (15 days-5 mg/kg). DZP was rapidly distributed in brain areas. Its concentrations and its kinetic parameters were not uniform in the different brain areas we studied. The results showed the highest content of DZP in the hypothalamus, followed by the nucleus caudatus and the colliculi. Our data presented the erythrocyte as a "deep compartment". Comparatively to the results obtained after single administration, this study showed an increase of the apparent elimination half-life. Indeed, one observes a 2 fold increase for the plasma, and a 3.5 fold increase for the cerebral compartment. In the three brain areas studied (nucleus caudatus, hippocampus, and cerebellum) we observed a linear relationship with plasmatic or erythrocytic levels (0.978 less than or equal to r less than or equal to 0.992). It seems important to be considered in clinical pharmacology.

Animals↗

PubMedDate not supplied

[Neuroendocrine effects of a sodium valproate and diazepam combination in the male rat].

The effects of chronic administration of sodium valproate (200 mg/Kg/d i.p.) and diazepam (5 mg/Kg/d i.m.) alone or in association on the plasma levels of the pituitary hormones (prolactin, FSH and LH) were studied in the m ale rat. Sodium valproate increases prolactin plasma levels. This effect is antagonized by diazepam. Both molecules do not affect FSH levels, whereas they increase LH levels when given alone or in association. This pharmacological data state precisely the hypothalamohypophysiotropic effects of valproate and diazepam during its association.

Animals↗