caa a22 4500 477126375 CHVBK 20180405111651.0 cr unu---uuuuu 170330e19970701xx s 000 0 eng 10.1023/A:1012143631873 doi (NATIONALLICENCE)springer-10.1023/A:1012143631873 The Disposition of Valproyl Glycinamide and Valproyl Glycine in Rats [Elektronische Daten] [Simcha Blotnik, Felix Bergman, Meir Bialer] Purpose. To investigate the disposition of valproyl glycinamide and valproyl glycine in rats and to compare it with that of valproic acid (VPA) and valpromide which were studied previously. Methods. The study was carried out by monitoring the brain and liver levels of valproyl glycinamide and valproyl glycine (as a function of time after iv dosing) in addition to the regular pharmacokinetic (PK) monitoring of plasma and urine levels of these compounds. Results. The following PK parameters were obtained for valproyl glycinamide and valproyl glycine, respectively: clearance, 7.1 and 16 ml/ min/kg; volume of distribution (Vss), 0.78 and 0.41 1/kg; half-life, 1.1 and 0.37 h; and mean residence time, 1.8 and 0.4 h. The ratios of AUCs of valproyl glycinamide of liver to plasma and brain to plasma were 0.70 and 0.66, respectively. The ratios of the AUCs of valproyl glycine of liver to plasma and brain to plasma were 0.19 and 0.02, respectively. Conclusions. Valproyl glycinamide distributes better in the brain than VPA, a fact which may contribute to its better anticonvulsant activity. Valproyl glycine was barely distributed in the brain, a fact which may explain its lack of anticonvulsant activity. In addition to the liver, the brain was found to be a minor metabolic site of the biotransformation of valproyl glycinamide to valproyl glycine. Plenum Publishing Corporation, 1997 valproyl glycinamide nationallicence valproyl glycine nationallicence pharmacokinetics nationallicence brain and liver distribution nationallicence Blotnik Simcha Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, P.O.B. 12065, 91120, Jerusalem, Israel aut Bergman Felix Department of Pharmacology, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, P.O.B. 12065, 91120, Jerusalem, Israel aut Bialer Meir Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, P.O.B. 12065, 91120, Jerusalem, Israel aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/7(1997-07-01), 873-878 0724-8741 14:7<873 1997 14 11095 https://doi.org/10.1023/A:1012143631873 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012143631873 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Blotnik Simcha Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, P.O.B. 12065, 91120, Jerusalem, Israel aut NATIONALLICENCE 700 1- Bergman Felix Department of Pharmacology, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, P.O.B. 12065, 91120, Jerusalem, Israel aut NATIONALLICENCE 700 1- Bialer Meir Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, P.O.B. 12065, 91120, Jerusalem, Israel aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/7(1997-07-01), 873-878 0724-8741 14:7<873 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer