Concentrations of Stiripentol in Children and Adults With Epilepsy

May, Theodor W.; Boor, Rainer; Mayer, Thomas; Jürgens, Uwe; Rambeck, B.; Holert, Nils; Korn-Merker, E; Brandt, Christian

doi:10.1097/ftd.0b013e31825dc4a6

Cited by 48 publications

(8 citation statements)

References 22 publications

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“…This study confirmed the Michaelis‐Menten pharmacokinetic profile of stiripentol that was previously described in adult healthy volunteers and people with epilepsy 24, 25. Only two adverse effects (one rhinitis and one pharyngitis) were observed, unlikely related to the treatment.…”

Section: Discussionsupporting

confidence: 89%

Audit of use of stiripentol in adults with Dravet syndrome

Balestrini

Sisodiya

2016

Acta Neurol Scand

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ObjectivesThere are very few data available in the literature on the use of stiripentol in adults with Dravet syndrome (DS). DS cases are increasingly recognized in adulthood, and more children with DS now survive to adulthood. The aim of the study was to document the effectiveness and tolerability of stiripentol in adults with DS.Material and methodsWe conducted an observational clinical audit in the epilepsy service of the National Hospital for Neurology and Neurosurgery, London (UK).ResultsWe included 13 adult subjects with DS (eight females, five males). The responder (defined as more than 50% reduction in all seizure types) rate was 3/13 (23%) at 36 months. The following other outcomes were reported: seizure exacerbation (3/13, 23%), no change (3/13, 23%), less than 50% reduction in seizures (2/13, 15%), more than 50% reduction in generalized tonic‐clonic seizures but no other seizure types (1/13, 8%), undefined response (1/13, 8%). The retention rate was 62% after 1 year and 31% after 5 years. Adverse effects were reported in 7/13 (54%): the most frequent were anorexia, weight loss, unsteadiness and tiredness. Withdrawal due to adverse effects occurred in 3/13 (23%).ConclusionsCompared with previous studies on children with DS, our results show a lower responder rate and a similar tolerability profile. Stiripentol can be effective with a good tolerability profile. Our audit is small, but supports the use of stiripentol in adults with DS when first‐line treatments are ineffective or not tolerated, in keeping with published guidelines.

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Section: Discussionsupporting

confidence: 89%

Audit of use of stiripentol in adults with Dravet syndrome

Balestrini

Sisodiya

2016

Acta Neurol Scand

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“…Although an assay to measure stiripentol levels is described, it is not indicated for therapeutic purposes by the manufacturer or regulatory bodies such as Health Canada, FDA or the EU. As such, it was not available for us for the purposes of this study (18).…”

Section: Discussionmentioning

confidence: 99%

Dosage Related Efficacy and Tolerability of Cannabidiol in Children With Treatment-Resistant Epileptic Encephalopathy: Preliminary Results of the CARE-E Study

et al. 2019

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Purpose: There is uncertainty regarding the appropriate dose of Cannabidiol (CBD) for childhood epilepsy. We present the preliminary data of seven participants from the Cannabidiol in Children with Refractory Epileptic Encephalopathy (CARE-E) study. Methods: The study is an open-label, prospective, dose-escalation trial. Participants received escalating doses of a Cannabis Herbal Extract (CHE) preparation of 1:20 Δ 9 -tetrahydrocannabinol (THC): CBD up to 10–12 mg CBD/kg/day. Seizure frequency was monitored in daily logs, participants underwent regular electroencephalograms, and parents filled out modified Quality of Life in Childhood Epilepsy (QOLCE) and Side Effect rating scale questionnaires. Steady-state trough levels (C ss, Min ) of selected cannabinoids were quantified. Results: All seven participants tolerated the CHE up to 10–12 mg CBD/kg/day and had improvements in seizure frequency and QOLCE scores. C SS, Min plasma levels for CBD, THC, and cannabichromene (CBC) showed dose-independent pharmacokinetics in all but one participant. C SS, Min CBD levels associated with a >50% reduction in seizures and seizure freedom were lower than those reported previously with purified CBD. In most patients, C SS, Min levels of THC remained lower than what would be expected to cause intoxication. Conclusion: The preliminary data suggest an initial CBD target dose of 5–6 mg/kg/day when a 1:20 THC:CBD CHE is used. Possible non-linear pharmacokinetics of CBD and CBC needs investigation. The reduction in seizure frequency seen suggests improved seizure control when a whole plant CHE is used. Plasma THC levels suggest a low risk of THC intoxication when a 1:20 THC:CBD CHE is used in doses up to 12 mg/kg CBD/kg/day.

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“…STP inhibits CYP3A4 and CYP2C19 engaged in the demethylation of the CLB active metabolite, leading to a two-fold increase in the concentration of the parent drug and from a three-to five-fold increase in concentration of its metabolite [167]. Plasma concentrations of other AEDs, including CBZ, PHB, PHT, VPA, diazepam, ESM and TGB, may be increased with STP co-administration [168][169][170][171]. Concomitant administration of CBD and STP may increase STP C max 1.3-fold and AUC 1.6-fold, while 7-OH-CBD and 7-COOH-CBD exposure were decreased by 29% and 13%, respectively [172].…”

Section: Stiripentolmentioning

confidence: 99%

Pharmacokinetic Drug–Drug Interactions among Antiepileptic Drugs, Including CBD, Drugs Used to Treat COVID-19 and Nutrients

Karaźniewicz−Łada

Główka

Mikulska

et al. 2021

IJMS

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Anti-epileptic drugs (AEDs) are an important group of drugs of several generations, ranging from the oldest phenobarbital (1912) to the most recent cenobamate (2019). Cannabidiol (CBD) is increasingly used to treat epilepsy. The outbreak of the SARS-CoV-2 pandemic in 2019 created new challenges in the effective treatment of epilepsy in COVID-19 patients. The purpose of this review is to present data from the last few years on drug–drug interactions among of AEDs, as well as AEDs with other drugs, nutrients and food. Literature data was collected mainly in PubMed, as well as google base. The most important pharmacokinetic parameters of the chosen 29 AEDs, mechanism of action and clinical application, as well as their biotransformation, are presented. We pay a special attention to the new potential interactions of the applied first-generation AEDs (carbamazepine, oxcarbazepine, phenytoin, phenobarbital and primidone), on decreased concentration of some medications (atazanavir and remdesivir), or their compositions (darunavir/cobicistat and lopinavir/ritonavir) used in the treatment of COVID-19 patients. CBD interactions with AEDs are clearly defined. In addition, nutrients, as well as diet, cause changes in pharmacokinetics of some AEDs. The understanding of the pharmacokinetic interactions of the AEDs seems to be important in effective management of epilepsy.

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Concentrations of Stiripentol in Children and Adults With Epilepsy

Abstract: Therapeutic drug monitoring of STP seems to be useful because of the wide variation of STP CDR, the nonlinear concentration-to-dose relationship, age-dependent pharmacokinetics, and drug-drug interactions.

Cited by 48 publications

References 22 publications

Audit of use of stiripentol in adults with Dravet syndrome

Audit of use of stiripentol in adults with Dravet syndrome

Dosage Related Efficacy and Tolerability of Cannabidiol in Children With Treatment-Resistant Epileptic Encephalopathy: Preliminary Results of the CARE-E Study

Pharmacokinetic Drug–Drug Interactions among Antiepileptic Drugs, Including CBD, Drugs Used to Treat COVID-19 and Nutrients

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