caa a22 4500 469026251 CHVBK 20180323132730.0 cr unu---uuuuu 170328e19920601xx s 000 0 eng 10.1007/BF01962698 doi (NATIONALLICENCE)springer-10.1007/BF01962698 Pisani Francesco First Neurological Clinic, University of Messina, 98013, Contessa-Messina, Italy aut Influence of co-medication on the metabolism of valproate [Elektronische Daten] [Francesco Pisani] Valproate is extensively metabolized in the liver and at least six main pathways which produce about 50 metabolites have been identified in man. The enzyme-inducing antiepileptic drugs phenobarbital, primidone, phenytoin and carbamazepine increase total valproate clearance by 30-85%, whereas cimetidine and the new anticonvulsant compound striripentol display a small inhibitory effect (10-20%). Both carbamazepine and phenytoin induce a two-fold increase in the formation of Δ4-valproate and stimulateω-oxidation andω-1-oxidation. Acetylsalicylic acid causes a fall of 60-70% in the content in the urine of the metabolites of theβ-oxidative pathway,i.e. Δ 2-valproate, 3-OH-valproate and 3-oxo-valproate, and an increase of glucuronidation (approximately 30%) andδ-dehydrogenation (approximately 20%). Stiripentol inhibits the formation clearance ofΔ 4-valproate by 30%. In the light of the possible therapeutic and toxic effects of some valproate metabolites, drug interactions with valproate at metabolic level may have important clinical implications. Royal Dutch Association for Advancement of Pharmacy, 1992 Acetylsalicylic acid nationallicence [Anticonvulsants nationallicence Biotransformation nationallicence Cimetidine nationallicence Drug interactions nationallicence Liver diseases nationallicence Metabolites nationallicence Pharmacokinetics nationallicence Valproic acid nationallicence Pharmaceutisch Weekblad Kluwer Academic Publishers 14/3(1992-06-01), 108-113 0031-6911 14:3<108 1992 14 11096 https://doi.org/10.1007/BF01962698 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF01962698 text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Pisani Francesco First Neurological Clinic, University of Messina, 98013, Contessa-Messina, Italy aut NATIONALLICENCE 773 0- Pharmaceutisch Weekblad Kluwer Academic Publishers 14/3(1992-06-01), 108-113 0031-6911 14:3<108 1992 14 11096 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer