Selected CSF biochemistry and gabapentin concentrations in the CSF and plasma in patients with partial seizures after a single oral dose of gabapentin.
Gabapentin (GBP) is a neutral amino acid and a GABA analog which in animal experimental models has shown a broad anticonvulsant spectrum. To evaluate the penetration of GBP into the CSF in humans as well as its possible effects on free and total GABA, homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA), a special investigation was performed as part of a placebo controlled add-on study of GBP in partial epilepsy. At the end of the 3-month double-blind period, 5 patients on placebo were given a single oral dose of GBP. Four patients received 600 mg and 1 patient 1200 mg GBP. CSF was collected immediately before and at 6, 24 and 72 h after the single dose. 5 ml of plasma was collected at 1, 2, 3, 6, 12, 24, 48 and 72 h. Plasma concentrations and plasma elimination half-life (4-6 h) of GBP were in agreement with the results of previous studies. The CSF/plasma concentration ratio of GBP 6 h after drug was 0.1. After 24 h, GBP could only be recovered in the CSF of the patient given 1200 mg. The CSF/plasma ratio at that time was 0.3. Free and total GABA concentrations did not change, but CSF 5-HIAA and HVA increased at 24 and 72 h post dose. The CSF/plasma ratio of gabapentin is similar to that of other amino acids.
Ben-Menachem
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Department of Neurology, University of Göteborg, Sweden.
Persson
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Hedner
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D000085:Acetates / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000494:pharmacology; D000284:Administration, Oral; D000328:Adult; D000588:Amines; D000927:Anticonvulsants / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003509:Cyclohexanecarboxylic Acids; D004828:Epilepsies, Partial / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D005260:Female; D000077206:Gabapentin; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008297:Male; D012701:Serotonin / Q000134:cerebrospinal fluid; D005680:gamma-Aminobutyric Acid / Q000134:cerebrospinal fluid
D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D006719:Homovanillic Acid