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  • Title: Vigabatrin extracellular pharmacokinetics and concurrent gamma-aminobutyric acid neurotransmitter effects in rat frontal cortex and hippocampus using microdialysis.
    Author: Tong X, Ratnaraj N, Patsalos PN.
    Journal: Epilepsia; 2009 Feb; 50(2):174-83. PubMed ID: 19016829.
    Abstract:
    PURPOSE: To investigate the pharmacokinetic interrelationship of vigabatrin in blood and the brain (frontal cortex vs. hippocampus) and to ascertain the relationship between brain extracellular vigabatrin concentrations and concurrent gamma-aminobutyric acid (GABA) concentrations. METHODS: Sprague-Dawley rats were implanted with a jugular vein catheter for blood sampling, and microdialysis probes in the frontal cortex and hippocampus for extracellular fluid (ECF) sampling. Vigabatrin was administered intraperitoneally at two different doses (500 and 1,000 mg/kg), and blood and ECF were collected at timed intervals up to 8 h. Rats were freely moving and behaving. Vigabatrin (sera and ECF) and GABA (ECF) concentrations were measured with use of high performance liquid chromatography (HPLC). RESULTS: Vigabatrin concentrations in blood rose linearly and dose-dependently, and vigabatrin rapidly appeared in the brain as evidenced by the detection of vigabatrin in the ECF of both the frontal cortex and hippocampus at time of first sampling (15 min). However, frontal cortex concentrations were twofold greater than those of the hippocampus. Furthermore, GABA concentrations increased five-fold in the frontal cortex but were unaffected in the hippocampus. In addition, GABA concentrations began to increase approximately 3 h after vigabatrin administration at a time when vigabatrin concentrations were in exponential decline. CONCLUSIONS: Vigabatrin distribution in the brain is region specific, with frontal cortex concentrations substantially greater than those seen in the hippocampus. Elevation of GABA concentrations did not reflect the concentration profile of vigabatrin but reflected its regional distribution.
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