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Disposition of sodium valproate in epileptic patients.
Author(s) -
Perucca E,
Gatti G,
Frigo GM,
Crema A,
Calzetti S,
Visintini D
Publication year - 1978
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1978.tb01663.x
Subject(s) - valproic acid , medicine , serum concentration , oral administration , anticonvulsant , pharmacokinetics , distribution (mathematics) , disposition , epilepsy , pharmacology , anesthesia , psychology , mathematical analysis , social psychology , mathematics , psychiatry
1 Serum levels of valproic acid have been determined at fixed intervals after the administration of single oral and intravenous doses (800 mg) to six epileptic patients receiving chronic treatment with other antiepileptic drugs. 2 Serum levels declined monoexponentially shortly after the intravenous administration. Biological half‐lives averaged 9.0 +/− 1.4 h (s.d.). Volumes of distribution were 0.175 +/− 0.025 l/kg. There was a statistically significant negative correlation between volumes of distribution and serum half‐lives (P less than 0.005). 3 After oral doses serum levels rose rapidly to peak values within 0.5–2 h. Biological availability was 96 +/− 9%. 4 Comparison with a previous study performed according to the same protocol in healthy volunteers showed significantly increased volumes of distribution and rates of elimination in the patients. Total serum clearance was 85% higher in the patients as compared to the healthy subjects (P less than 0.001). Possible explanations for these findings are discussed.