Br. J. clin. Pharmac. (1978), 5,495-499
DISPOSITION OF SODIUM VALPROATE IN EPILEPTIC PATIENTS E. PERUCCA,* G. GATTI, G.M. FRIGO & A. CREMA Institute of Medical Pharmacology, University of Pavia, Pavia, Italy
S. CALZETTI & D.VISINTINI Clinic for Nervous Diseases, University of Parma, Parma, Italy
I 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 1/kg. There was a statistically significant negative correlation between volumes of distribution and serum half-lives (P < 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
DISPOSITION OF SODIUM VALPROATE IN EPILEPTIC PATIENTS E. PERUCCA,* G. GATTI, G.M. FRIGO & A. CREMA Institute of Medical Pharmacology, University of Pavia, Pavia, Italy
S. CALZETTI & D.VISINTINI Clinic for Nervous Diseases, University of Parma, Parma, Italy
I 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 1/kg. There was a statistically significant negative correlation between volumes of distribution and serum half-lives (P < 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
