Investigation of the metabolism of rufinamide and its interaction with valproate.

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Williams ET, Carlson JE, Lai WG, Wong YN, Yoshimura T, Critchley DJ, Narurkar M

Investigation of the metabolism of rufinamide and its interaction with valproate.

Drug Metab Lett. 2011 Dec;5(4):280-9.

PubMed ID

22022867 [ View in PubMed

]

Abstract

Rufinamide was evaluated in vitro to determine which enzyme(s) are responsible for rufinamide hydrolysis and whether valproate, one of its metabolites (valproyl-CoA), and/or the rufinamide hydrolysis product (CGP 47292) could inhibit hydrolysis. Rufinamide hydrolysis was mediated primarily by human carboxylesterase (hCE) 1 and was nonsaturable up to 500 muM. Two-thirds of rufinamide hydrolysis was estimated to occur in human microsomes and one-third in cytosol. Valproate was a selective inhibitor for hCE1 compared to hCE2 and inhibition had a greater impact on rufinamide hydrolysis in microsomes than in cytosol. Valproyl-CoA caused similar inhibition of rufinamide hydrolysis in both microsomes and cytosol. Carboxylesterases were not significantly inhibited by CGP 47292. Inhibition of in vitro rufinamide hydrolysis by valproate could offer an explanation for the observed in vivo drug-drug interaction between the two antiepileptic drugs.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Rufinamide	Liver carboxylesterase 1	Protein	Humans	Unknown	Substrate	Details

Drug Interactions

Drugs	Interaction
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Rufinamide Valproic acid	The serum concentration of Rufinamide can be increased when it is combined with Valproic acid.