Carbamazepine Dose Requirements During Stiripentol Therapy: Influence of Cytochrome P‐450 Inhibition Stiripentol

Kerr, Bradley M.; Martínez‐Lage, J. M.; Viteri, C.; Tor, Jacques; Eddy, A C

doi:10.1111/j.1528-1157.1991.tb05254.x

Cited by 38 publications

(11 citation statements)

References 19 publications

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“…The clearance of CBZ during STP therapy in 7 pediatric patients (0.91 ? 0.18 L/day/kg) was similar to the value previously reported (Kerr et al, 1991) in 7 adult patients (0.88 ? 0.20 L/day/kg).…”

Section: Patient Experiencesupporting

confidence: 92%

Stiripentol in Atypical Absence Seizures in Children: An Open Trial

et al. 1993

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Stiripentol (STP) was added to the antiepileptic drug (AED) regimen of 10 patients with uncontrolled atypical absence seizures (more than one seizure a day). Seven boys and three girls aged 6-16 years participated in the study. Concomitant AEDs included various combinations of phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA). Parents counted daily seizures over a 4-week baseline period before institution of STP, and in a 20-week period during STP therapy. To compensate for drug interactions, doses of other AEDs were adjusted during STP administration to keep serum levels close to levels of the baseline period. Maintenance doses of STP were 1,000-3,000 mg/day, giving serum levels of 4-22 micrograms/mL. All patients experienced a decrease in atypical absence seizures. Average decrease was 70% (range 5-95%). Side effects experienced by some patients were dose related and included anorexia, nausea, vomiting, and lethargy. In only 1 patient did an adverse effect (vomiting) require discontinuation of STP. We conclude that STP shows promise in treatment of atypical absence seizures in children, and further trials are warranted.

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Section: Patient Experiencesupporting

confidence: 92%

Stiripentol in Atypical Absence Seizures in Children: An Open Trial

et al. 1993

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“…This is associated, as pointed out previously, with the methylenedioxyphenyl ring system in the stiripentol molecule that is metabolized to catechol derivatives, leading to the inhibition of CYP 450 enzymes [37][38][39] . The existing evidences point to the inhibitory effects of stiripentol against many forms of CYP 450 in vitro and CYPs 1A2 or 3A4 in vivo [40] .…”

Section: Interactions With Other Aedsmentioning

confidence: 97%

“…• Decreased carbamazepine clearance by 50% and its metabolic transformation to carbamazepine-10,11-epoxide [38] . Interestingly, there is no further infl uence of stiripentol on the subsequent metabolism of the epoxide metabolite.…”

Section: Interactions With Other Aedsmentioning

confidence: 98%

Stiripentol – characteristic of a new antiepileptic drug

Czuczwar

Trojnar

Gergont

et al. 2008

Expert Opinion on Drug Discovery

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Stiripentol represents a group of drugs indirectly enhancing GABA-ergic neurotransmission and it exerts a protective activity in some experimental seizure models, including maximal electroshock (MES)-, pentylenetetrazol-, bicuculline-, strychnine-, and cocaine-induced convulsions. The drug potently inhibits metabolism of other antiepileptic drugs, significantly elevating their plasma and brain concentrations. This requires dosage adjustments of the concomitant antiepileptic drugs used in combination. In the form of an add-on therapy, stiripentol has proved to be effective in partial and atypical absence epilepsies. Considering its particular efficacy against severe myoclonic seizures in infancy (Dravet's syndrome), stiripentol has been awarded an orphan drug status for an adjunctive therapy of this difficult-to-treat condition.

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“…11O,113] carbamazepine,l109, [113][114][115][116] phenobarbital, [107,117] primidone [87,107] and valproic acid.l1l8-120] Most of these interactions are clinically important and may require adjustments in the dosage of associated drugs.…”

Section: Stiripentolmentioning

confidence: 99%

The Clinical Pharmacokinetics of the Newer Antiepileptic Drugs

Perucca

Bialer

1996

Clinical Pharmacokinetics

164

101

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Following the introduction of felbamate, gabapentin, lamotrigine, oxcarbazepine and vigabatrin in the early 1990s, other new antiepileptic drugs have been advancing in clinical development. Those most extensively evaluated to date include topiramate, zonisamide and tiagabine. Topiramate, licensed recently in the UK, acts multifactorially through the blockade of sodium channels and kainate/AMPA receptors, enhancement of gamma-aminobutyric acid (GABA)ergic transmission and inhibition of carbonic anhydrase. It is well absorbed from the gastrointestinal tract and negligibly bound to plasma proteins. When used as a monotherapy, topiramate is eliminated primarily in the urine in an unchanged form with a half-life of 20 to 30 hours; elimination is faster in patients receiving concurrent medication with enzyme-inducing anticonvulsants, in whom the extent of biotransformation becomes more prominent. Zonisamide, which has been commercially available in Japan for some years, also has a multifactorial mode of action, possibly involving the blockade of sodium channels, T-type calcium channels and inhibition of carbonic anhydrase. It is rapidly absorbed, 50% bound to plasma proteins and is eliminated predominantly by biotransformation; zonisamide has a half-life of 50 to 70 hours in monotherapy patients, or 25 to 35 hours in patients comedicated with enzyme-inducing anticonvulsants. Tiagabine, a nipecotic acid derivative which inhibits GABA reuptake, is rapidly and completely absorbed after oral intake. It is highly (96%) bound to plasma proteins and it is eliminated primarily by cytochrome P450 3A-mediated oxidation, with a half-life of about 7 hours in healthy volunteers. Tiagabine metabolism is also enhanced by concurrent medication with enzyme-inducing anticonvulsants, resulting in a need to use dosages larger than those required in monotherapy or valproic acid (sodium valproate)-treated patients. Additional investigational antiepileptic agents included in this article are rufinamide (CGP 33101), fosphenytoin, levetiracetam, losigamone, remacemide and stiripentol. All these drugs have undergone early characterisation with respect to pharmacokinetic features and interaction potential.

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Carbamazepine Dose Requirements During Stiripentol Therapy: Influence of Cytochrome P‐450 Inhibition Stiripentol

Cited by 38 publications

References 19 publications

Stiripentol in Atypical Absence Seizures in Children: An Open Trial

Stiripentol in Atypical Absence Seizures in Children: An Open Trial

Stiripentol – characteristic of a new antiepileptic drug

The Clinical Pharmacokinetics of the Newer Antiepileptic Drugs

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