Elsevier

Biochemical Pharmacology

Volume 37, Issue 19, 1 October 1988, Pages 3619-3622
Biochemical Pharmacology

Ex vivo inhibition of rat brain cytochrome P-450 activity by stiripentol

https://doi.org/10.1016/0006-2952(88)90393-0Get rights and content

Abstract

Stiripentol is an anti-epileptic drug of novel structure with previously demonstrated strong in vitro inhibitory activity on rat cerebral cytochrome P-450 mediated naphthalene hydroxylation [6]. When administered to rats as a single i.p. dose, the drug is presently shown to have the same in vitro effect. Maximal inhibition is seen 2 hr after administration, but at this time the brain concentrations of intact drug, although peaking, appear too low (ca. 11 μg/g tissue) to account for the intensity of the effect seen in vitro. This suggests in vitro activation to a metabolic intermediate forming a complex with cerebral cytochrome P-450, which 2 hr after dosing is fully insensitive to stiripentol added to incubates. Restoration of enzymic activity and of sensitivity to added stiripentol occurs progressively and is practically complete 24 hr after dosing.

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