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.

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PubMedDate not supplied

Ocular pharmacokinetics of calcium, chloride and sulphate ions after instillation in the rabbit.

The ionic environment of the eye is involved in major biochemical processes which are essential for preserving the integrity of cornea and lens. The purpose of the present study was to determine the intra-ocular penetration and the pharmacokinetic parameters of calcium, chloride and sulphate ions in the cornea, iris-ciliary body (ICB) and lens, after administration by instillation in the rabbit eye. In order to extrapolate our results to the processes occurring in man, we followed a precise instillation protocol using a low volume (5 microliters) of 45Calcium, 36Chloride and 35Sulphate, which is less than the lacrimal volume determined during the palpebral closing and performing manual blinking at a frequency of 2 min-1. The results indicate an immediate trans-corneal permeability and a rapid ocular distribution of these ions. We observe that, relative to dose, an important percentage of calcium (67.20 per cent) was entrapped in the cornea; this parameter was less important for chloride (10.19 per cent) and for sulphate ions (3.25 per cent). These values are in agreement with those predicted theoretically for trans-corneal penetration by such compounds. On the other hand, the total degrees of penetration by chloride and sulphate ions in ICB (1.40 per cent and 0.90 per cent, respectively) and lens (0.35 per cent and 0.41 per cent, respectively) are quite similar. Calcium retention is much higher in these tissues (25.39 per cent in ICB and 16.03 per cent in lens).(ABSTRACT TRUNCATED AT 250 WORDS)

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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.

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