Pharmacokinetics and Anticonvulsant Activity of Three Monoesteric Prodrugs of Valproic Acid |
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Authors: | Badir Khalil Haj-Yehia Abdulla Vree Tom B. van der Kleijn Eppo Bialer Meir |
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Affiliation: | (1) Department of Pharmacy, School of Pharmacy, Hebrew University of Jerusalem, P.O. Box 12065, Jerusalem, Israel;(2) Department of Clinical Pharmacy, St. Radboud Hospital, Catholic University of Nijmegen, Postbus 9101, 6800 HB Nijmegen, The Netherlands |
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Abstract: | The pharmacokinetics of valproic acid (VPA) were compared in dogs with those of the prodrugs ethyl valproate (E-VPA), trichloroethyl valproate (T-VPA), and valproyl valproate (V-VPA). Valproic acid, E-VPA, T-VPA, and V-VPA were administered intravenously and orally to six dogs at equimolar doses. The three VPA prodrugs were rapidly converted to VPA. The biotransformation was complete in the case of E-VPA and T-VPA but was only partial in the case of V-VPA. Because of the rapid conversion to the parent drug, after administration of the prodrugs, VPA plasma levels did not yield a sustained-release profile. Further, the anticonvulsant activity of prodrugs was compared in mice to that of VPA and valpromide (VPD). The anticonvulsant activity of E-VPA, T-VPA, and V-VPA was less than that of VPA. |
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Keywords: | valproic acid esteric prodrugs pharmacokinetics |
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