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Catherine Chiron - One of the best experts on this subject based on the ideXlab platform.
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Stiripentol for the treatment of seizures associated with Dravet syndrome
Expert Review of Neurotherapeutics, 2019Co-Authors: Catherine ChironAbstract:Introduction: Stiripentol is an orphan drug approved for the treatment of seizures associated with Dravet syndrome (since 2007 in Europe). Therapeutic options recently grew in this rare and severe ...
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do children with dravet syndrome continue to benefit from Stiripentol for long through adulthood
Epilepsia, 2018Co-Authors: Catherine Chiron, Marie Helias, Anna Kaminska, Cecile Laroche, Bertrand De Toffol, O Dulac, Rima NabboutAbstract:Objective To evaluate continuing Stiripentol treatment in adulthood in Dravet syndrome (DS). Method Longitudinal data were collected from the last visit prior to age 15 years (V15 y ) to the last visit in adulthood (Vadult ) in the 40 DS patients (32 typical, eight atypical) of a French historical cohort (Paris) of subjects who continued Stiripentol from childhood or adolescence to adulthood. Results At Vadult (18-40 years, median = 23 years), all the patients were still receiving Stiripentol (exposure = 3-24 years, median = 18 years), associated with clobazam (40/40), valproate (39/40), and topiramate (21/40). Between V15 y and Vadult , Stiripentol was interrupted in five patients (two for adverse events) but reintroduced following seizure aggravation. Loss of appetite affected 15 of 40 patients but resolved after reducing the dose of Stiripentol or valproate; no other new Stiripentol-related adverse events were reported. Mean Stiripentol dose was progressively decreased from 39 to 25 mg/kg/d (P = 0.0002), whereas clobazam (0.27 mg/kg/d) and valproate (14 mg/kg/d) remained stable. At Vadult , 37 of 40 patients still had generalized tonic-clonic seizures, but none still had status epilepticus (vs three at V15 y ) and only one had myoclonia. During adulthood, generalized tonic-clonic seizure frequency and duration continued to decrease (P = 0.02, P = 0.008) and 10 patients experienced seizure-free periods ≥ 1 years (up to 5 years). All patients already had intellectual disability at V15 y , but retardation was more severe at Vadult (P = 0.03). Furthermore, neurological/gait condition had declined (two patients became bedridden) and behavior had worsened (P 15 years) and the DS patients treated from adult age or Stiripentol-naive subjects reported in the literature. Significance The efficacy and safety of the Stiripentol/valproate/clobazam combination started at pediatric age are maintained at very long term during adulthood. Such prolonged Stiripentol therapy tends to positively impact the late prognosis of epilepsy, especially when initiated before adolescence.
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population pharmacokinetics of Stiripentol in paediatric patients with dravet syndrome treated with Stiripentol valproate and clobazam combination therapy
Clinical Pharmacokinectics, 2018Co-Authors: Elisabeth Rey, Sophie Peigne, Stephanie Chhun, Michel Tod, Christelle Rodrigues, Catherine ChironAbstract:The aim of this study was to describe the pharmacokinetics of Stiripentol in children with Dravet syndrome and to determine the concentrations of Stiripentol achieved in this population for the usual 25 mg/kg twice-daily dose. Thirty-five children with epilepsy were included in a prospective population pharmacokinetic study (using MONOLIX software). Four blood samples were drawn per patient. Stiripentol area under the plasma concentration–time curve (AUC) values and trough concentrations were simulated for 7000 theoretical children weighing between 10 and 70 kg for the 25 mg/kg twice-daily dose. The pharmacokinetics of Stiripentol was described using a one-compartment model with zero-order absorption and first-order elimination. The apparent clearance (CL/F) and apparent volume of distribution (V d/F) of Stiripentol were related to body weight by allometric equations. A dose-dependent non-linearity was also observed with an allometric model relating CL/F to the weight-normalised dose. Mean population estimates (% inter-individual variability) were 4.2 L/h (21%) for CL/F and 82 L (25%) for V d/F. The AUC of Stiripentol increased by 300% when body weight increased from 10 to 70 kg. This population pharmacokinetic model of Stiripentol in children with Dravet syndrome confirmed the dose-dependent non-linearity that has been evidenced in adults. It also supported that a 25 mg/kg twice-daily dose might lead to excessive exposure in children >30 kg, suggesting an eventual dose adjustment during adolescence. This study is part of the STIPOP study (EUDRACT number: 2007-001784-30).
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Stiripentol and vigabatrin current roles in the treatment of epilepsy
Expert Opinion on Pharmacotherapy, 2016Co-Authors: Catherine ChironAbstract:ABSTRACTIntroduction: Stiripentol and vigabatrin are the two anticonvulsant drugs currently approved in severe infantile-onset epilepsies, respectively Dravet syndrome and infantile spasms.Areas covered: For both, the indication was discovered by chance thanks to an exploratory study. Both demonstrated indisputable efficacy through randomized-controlled trials. Stiripentol as adjunctive therapy to clobazam and valproate performed better than placebo, and vigabatrin as first-line monotherapy better than the reference steroid therapy in spasms due to tuberous sclerosis. At one-year treatment vigabatrin and steroids were equally efficient in the other etiologies of spasms. However, it took more than 20 years for both drugs to be approved world-wide.Expert opinion: Stiripentol suffered from pharmacokinetic potentiation of clobazam, thus raising the question whether it was efficient per se. Finally, animal models and pharmacogenetic data on CYP2C19 confirmed its specific anticonvulsant effect. Stiripentol (in ...
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reassessment of Stiripentol pharmacokinetics in healthy adult volunteers
Epilepsy Research, 2014Co-Authors: Sophie Peigne, Catherine Chiron, Gerard Pons, O Dulac, Elisabeth Rey, Marieemmanuelle Le Guern, Vincent JullienAbstract:Because children who have been receiving Stiripentol for the treatment of Dravet syndrome for more than 10 years are now becoming young adults, it is important to accurately characterize Stiripentol pharmacokinetics in this age range. A double-blind placebo-controlled dose ranging study was therefore conducted to investigate the pharmacokinetics and tolerability of Stiripentol in 12 healthy volunteers. Each subject received 3 single doses of Stiripentol (500, 1000, and 2000 mg) separated by a wash-out period of 1 week. Pharmacokinetics of Stiripentol was analyzed for each dose by non-compartmental analysis. Median area under the curve (AUC), terminal elimination half-life (t1/2,z) and maximal concentration (Cmax) were calculated for between-dose comparison. Safety was evaluated based on both clinical and biological criteria. Oppositely to previous results, there was no concentration rebounds in the elimination phase, which could be the consequence of the food intake. A more than proportional increase in the AUC was observed, associated with a significant increase in the t1/2,z, for increasing doses (median AUC of 8.3, 31 and 88 mgh/L, and median t1/2,z of 2, 7.7 and 10h for the 500, 1000, and 2000 mg doses respectively), which confirmed the Michaelis-Menten pharmacokinetics of Stiripentol. However, dose-normalized Cmax did not significantly vary between doses. Median Michaelis-Menten parameters were 117 mg/h for Vmax and 1.9 mg/L for Km. No safety concern was observed during the study. The present study allowed a better characterization of the disposition phase of Stiripentol and confirmed its non-linear pharmacokinetic behaviour. Further pharmacokinetic/pharmacodynamic studies would be useful to determine the optimal dose of Stiripentol for the treatment of Dravet patients in adulthood.
Leon Aarons - One of the best experts on this subject based on the ideXlab platform.
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a physiologically based pharmacokinetic model for clobazam and Stiripentol in adults and children
Pharmaceutical Research, 2015Co-Authors: Kayode Ogungbenro, Leon AaronsAbstract:To develop a physiologically based pharmacokinetic model in adults and children for clobazam, its active metabolite norclobazam and Stiripentol and to account for significant clinical interaction that has been reported when clobazam and Stiripentol are co-administered. A PBPK model with ten compartments was developed. An in vitro-in vivo extrapolation technique was used to scale clearance in children for clobazam and norclobazam and clearance parameters for Stiripentol were obtained from fitting. Other drug and system parameters were obtained from the literature. The tissue/blood partition coefficients adequately predict observed volume of distribution for clobazam and Stiripentol. In a clinical study in children where clobazam was administered alone and co-administered with Stiripentol, the predicted and observed minimum concentration at steady state (mean and 95% confidence interval) during clobazam monotherapy were 0.19 (0.05–0.49 mg/L) and 0.20 (0.17–0.23 mg/L), respectively, and predicted and observed norclobazam concentrations were 0.49 (0.16–1.38 mg/L) and 0.95 (0.91–0.99 mg/L), respectively. From an interaction study with Stiripentol the predicted Stiripentol concentration was 10.12 (2.51–39.36 mg/L) and the observed concentration was 10.0 (8.3–11.7 mg/L); the predicted clobazam concentration was 0.29 (0.07–1.05 mg/L) and the observed concentration was 0.31 (0.24–0.38 mg/L); and the predicted norclobazam concentration was 2.30 (0.45–5.53 mg/L) and the observed concentration was 4.32 (3.77–4.87 mg/L). The PBPK model adequately described observed data and the extent of interaction between clobazam/norclobazam and Stiripentol.
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A Physiologically Based Pharmacokinetic Model for Clobazam and Stiripentol in Adults and Children
Pharmaceutical Research, 2014Co-Authors: Kayode Ogungbenro, Leon AaronsAbstract:Purpose To develop a physiologically based pharmacokinetic model in adults and children for clobazam, its active metabolite norclobazam and Stiripentol and to account for significant clinical interaction that has been reported when clobazam and Stiripentol are co-administered.
Gerard Pons - One of the best experts on this subject based on the ideXlab platform.
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reassessment of Stiripentol pharmacokinetics in healthy adult volunteers
Epilepsy Research, 2014Co-Authors: Sophie Peigne, Catherine Chiron, Gerard Pons, O Dulac, Elisabeth Rey, Marieemmanuelle Le Guern, Vincent JullienAbstract:Because children who have been receiving Stiripentol for the treatment of Dravet syndrome for more than 10 years are now becoming young adults, it is important to accurately characterize Stiripentol pharmacokinetics in this age range. A double-blind placebo-controlled dose ranging study was therefore conducted to investigate the pharmacokinetics and tolerability of Stiripentol in 12 healthy volunteers. Each subject received 3 single doses of Stiripentol (500, 1000, and 2000 mg) separated by a wash-out period of 1 week. Pharmacokinetics of Stiripentol was analyzed for each dose by non-compartmental analysis. Median area under the curve (AUC), terminal elimination half-life (t1/2,z) and maximal concentration (Cmax) were calculated for between-dose comparison. Safety was evaluated based on both clinical and biological criteria. Oppositely to previous results, there was no concentration rebounds in the elimination phase, which could be the consequence of the food intake. A more than proportional increase in the AUC was observed, associated with a significant increase in the t1/2,z, for increasing doses (median AUC of 8.3, 31 and 88 mgh/L, and median t1/2,z of 2, 7.7 and 10h for the 500, 1000, and 2000 mg doses respectively), which confirmed the Michaelis-Menten pharmacokinetics of Stiripentol. However, dose-normalized Cmax did not significantly vary between doses. Median Michaelis-Menten parameters were 117 mg/h for Vmax and 1.9 mg/L for Km. No safety concern was observed during the study. The present study allowed a better characterization of the disposition phase of Stiripentol and confirmed its non-linear pharmacokinetic behaviour. Further pharmacokinetic/pharmacodynamic studies would be useful to determine the optimal dose of Stiripentol for the treatment of Dravet patients in adulthood.
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severe myoclonic epilepsy in infancy a systematic review and a meta analysis of individual patient data
Epilepsia, 2008Co-Authors: Behrouz Kassai, Catherine Chiron, E Rey, O Dulac, Segolene Augier, Michel Cucherat, Francois Gueyffier, Renzo Guerrini, Julien Vincent, Gerard PonsAbstract:Severe myoclonic epilepsy in infancy (SMEI) is a rare, but severe disorder with seizures typically resistant to conventional antiepileptic drugs. The objective of the present study was to systematically review the literature on the available treatments for SMEI. Databases searched included Medline, Embase, and Cochrane. We used a fixed effect model to summarize the odds ratio of seizures rates and a logistic model to evaluate the influence of patient characteristics on treatment effect. We found 23 uncontrolled studies and 2 randomized controlled trials (RCTs) that compared Stiripentol with placebo. Overall, 64 children aged between 3 and 20 years were included in the two RCTs. The odds ratio of responding to Stiripentol relative to placebo was 32 (CI: 6.2, 161) and Stiripentol reduced seizure rate by 70% (93%; 47%). The multivariate analysis does not suggest any differences within subgroups of participants and cotherapy. Results of uncontrolled studies in children with SMEI are potentially biased and do not provide valid information on the benefits and harms of treatments. The two RCTs identified, however, were performed with the same objectives and design and showed that seizure frequency is greatly reduced by Stiripentol in children with SMEI after 2 months of treatment.
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Stiripentol in childhood partial epilepsy randomized placebo controlled trial with enrichment and withdrawal design
Journal of Child Neurology, 2006Co-Authors: Catherine Chiron, Philippe Dathis, J Vincent, Elisabeth Rey, Olivier Dulac, Sylvie Tonnelier, Marielucie Brunet, Agnes Tran, Gerard PonsAbstract:Stiripentol, a new antiepileptic drug inhibiting cytochrome P450-enzymes, suggested some efficacy when combined with carbamazepine in an open trial in refractory partial epilepsy of childhood. Our objective was to test these results in a placebo-controlled trial. To limit the number of patients included, we used an enrichment and withdrawal design. Among the 67 children entered in a 4-month open add-on Stiripentol study following a 1-month single-blind placebo baseline, the 32 responders were randomized for 2 months either to continue Stiripentol (n = 17) or to withdraw to placebo (n = 15). If seizures increased by at least 50% after randomization compared with baseline, the patients dropped out (primary end point): there were six patients on Stiripentol and eight patients on placebo (not significant). However, a decrease in seizure frequency compared with baseline (secondary end point) was greater on Stiripentol (-75%) than on placebo (-22%) (P < .025). Twelve patients experienced at least one adverse event on Stiripentol (71%) compared with four patients on placebo (27%); none were reported as severe. The combination of Stiripentol and carbamazepine proved to reduce seizure frequency in children with refractory partial epilepsy, although it failed to show a significant impact according to the escape criteria selected as the primary end point in the present study, for ethical reasons.
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in vitro and in vivo inhibitory effect of Stiripentol on clobazam metabolism
Drug Metabolism and Disposition, 2006Co-Authors: Carole Giraud, Catherine Chiron, Jeanmarc Treluyer, Gerard Pons, Elisabeth Rey, J Vincent, Agnes TranAbstract:A metabolic interaction between Stiripentol (STP), an anticonvulsant agent that inhibits the activity of several cytochromes P450 (P450s), and clobazam (CLB), a 1,5-benzodiazepine, used in association with STP in severe myoclonic epilepsy in infancy was observed in vivo. This interaction was characterized in vitro using cDNA-expressed CYP3A4 and CYP2C19 (main P450 involved in CLB metabolism) to calculate K(i) and IC(50) of Stiripentol in comparison with ketoconazole (CYP3A4 inhibitor) and omeprazole (CYP2C19 inhibitor). STP inhibited N-demethylation of CLB to N-desmethylclobazam (NCLB) mediated by CYP3A4 (noncompetitively) and CYP2C19 (competitively) with K(i) = 1.59 +/- 0.07 and 0.516 +/- 0.065 microM and IC(50) = 1.58 microM [95% confidence interval (CI95%) = 1.20-2.08] and 3.29 microM (CI95% = 1.87-5.79), respectively. STP inhibited also more strongly the 4'-hydroxylation of NCLB to 4'-hydroxy-N-desmethylclobazam by CYP2C19 [competitive interaction with K(i) = 0.139 +/- 0.025 microM and IC(50) = 0.276 microM (CI95% = 0.206-0.371)]. The inhibitory effect of STP on CLB demethylation by CYP3A4 was much weaker than that of ketoconazole [IC(50) = 0.023 microM (CI95% = 0.016-0.033)], whereas its effect on NCLB hydroxylation by CYP2C19 was much higher than that of omeprazole [IC(50) = 2.99 microM (CI95% = 2.11-4.24)]. The major in vitro inhibitory effect of STP on CLB metabolism and mostly on NCLB biotransformation is consistent with the changes in vivo in CLB and NCLB plasma concentrations in children treated by the association CLB/STP.
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inhibitory effect of Stiripentol on carbamazepine and saquinavir metabolism in human
British Journal of Clinical Pharmacology, 2003Co-Authors: N Cazali, A Tran, Jeanmarc Treluyer, E Rey, Philippe Dathis, J Vincent, Gerard PonsAbstract:Aims To characterize the in vitro and in vivo inhibitory effect of Stiripentol, a new anticonvulsant, on the metabolism of carbamazepine and saquinavir, which are substrates of CYP3A4. Methods Human liver microsomes and cDNA-expressed CYP enzymes were used for the in vitro experiments. Pharmacokinetic data from epileptic children and healthy adults were used for the carbamazepine and saquinavir in vivo studies, respectively. Results Carbamazepine biotransformation to its 10,11-epoxide by human liver microsomes (Vmax = 10.3 nmol min−1 nmol−1 P450, apparent Km = 362 µm), cDNA-expressed CYP3A4 (Vmax = 1.17 nmol min−1 nmol−1 P450, apparent Km = 119 µm) and CYP2C8 (Vmax = 0.669 nmol min−1 nmol−1 P450, apparent Km = 757 µm) was inhibited by Stiripentol (IC50 14, 5.1, 37 µM and apparent Ki 3.7, 2.5, 35 µm, respectively). Saquinavir biotransformation to its major metabolite M7 by human liver microsomes (Vmax = 5.7 nmol min−1 nmol−1 P450, apparent Km = 0.79 µm) was inhibited by Stiripentol (IC50 163 µM, apparent Ki 86 µm). In epileptic children treated with carbamazepine and Stiripentol, the plasma concentration ratio of carbamazepine epoxide/carbamazepine was decreased by 65%. The in vivo apparent Ki for Stiripentol ranged from 10.5 to 41.4 µm. The pharmacokinetics of saquinavir was not modified by Stiripentol in healthy adults. The 95% confidence intervals for the difference for Cmax and AUC of saquinavir between the placebo and Stiripentol phase were (−39.8, 39.8) and (−33.2, 112), respectively. Conclusions These results showed that Stiripentol was a weak inhibitor of saquinavir metabolism both in vitro and in vivo. In contrast, Stiripentol is a potent inhibitor of carbamazepine 10,11-epoxide formation in vitro and in vivo in epileptic patients.
Doug Coyle - One of the best experts on this subject based on the ideXlab platform.
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economic evaluation of cannabinoid oil for dravet syndrome a cost utility analysis
PharmacoEconomics, 2020Co-Authors: Jesse Elliott, Blathnaid Mccoy, Tammy Clifford, George A Wells, Beth K Potter, Doug CoyleAbstract:Cannabinoid oils are being increasingly used to treat Dravet syndrome, yet the long-term costs and outcomes of this approach are unknown. Thus, we examined the cost effectiveness of cannabinoid oil as an adjunctive treatment (added to clobazam and valproate), compared with adjunctive Stiripentol or with clobazam and valproate alone, for the treatment of Dravet syndrome in children. We performed a probabilistic cost-utility analysis from the perspective of the Canadian public health care system, comparing cannabinoid oil and Stiripentol (both on a background of clobazam and valproate) with clobazam and valproate alone. Costs and quality-adjusted life-years (QALYs) were estimated using a Markov model that followed a cohort of children aged from 5 to 18 years through model states related to seizure frequency. Model inputs were obtained from the literature. The cost effectiveness of adjunctive cannabinoid oil, adjunctive Stiripentol, and clobazam/valproate alone was assessed through sequential analysis. The influence of perspective and other assumptions were explored in scenario analyses. All costs are expressed in 2019 Canadian dollars, and costs and QALYs were discounted at a rate of 1.5% per year. The incremental cost per QALY gained with the use of adjunctive cannabinoid oil, from the health care system perspective, was $32,399 compared with clobazam and valproate. Stiripentol was dominated by cannabinoid oil, producing fewer QALYs at higher costs. At a willingness-to-pay threshold of $50,000, cannabinoid oil was the optimal treatment in 76% of replications. From a societal perspective, cannabinoid oil dominated Stiripentol and clobazam/valproate. The interpretation of the results was insensitive to model and input assumptions. Compared with clobazam/valproate, adjunctive cannabinoid oil may be a cost-effective treatment for Dravet syndrome, if a decision maker is willing to pay at least $32,399 for each QALY gained. The opportunity costs of continuing to fund Stiripentol, but not cannabinoid oil, should be considered.
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economic evaluation of Stiripentol for dravet syndrome a cost utility analysis
PharmacoEconomics, 2018Co-Authors: Jesse Elliott, Blathnaid Mccoy, Tammy Clifford, George A Wells, Doug CoyleAbstract:Background Dravet syndrome is a catastrophic form of pediatric treatment-resistant epilepsy with few effective treatment options. Stiripentol is approved for use in Canada for treatment of Dravet syndrome, but the associated long-term costs and benefits have not been well-studied and its cost effectiveness is unclear.
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economic evaluation of Stiripentol for dravet syndrome a cost utility analysis
PharmacoEconomics, 2018Co-Authors: Jesse Elliott, Blathnaid Mccoy, Tammy Clifford, George A Wells, Doug CoyleAbstract:Dravet syndrome is a catastrophic form of pediatric treatment-resistant epilepsy with few effective treatment options. Stiripentol is approved for use in Canada for treatment of Dravet syndrome, but the associated long-term costs and benefits have not been well-studied and its cost effectiveness is unclear. The aim of this study was to evaluate the cost effectiveness of Stiripentol as an adjunctive treatment to clobazam and valproate for treatment of Dravet syndrome from the perspective of the Canadian public healthcare payer. A cost-utility analysis was performed to estimate the costs and quality-adjusted life-years (QALYs) associated with adjunctive Stiripentol treatment compared with clobazam and valproate alone in children with Dravet syndrome. Transition probabilities, drug efficacy, utility weights, and costs were obtained from a review of the literature. Probabilistic analyses were conducted using a Markov model with health states related to seizure frequency. A 10-year horizon was used. The incremental cost per QALY gained (incremental cost-effectiveness ratio [ICER]) for adjunctive use of Stiripentol was calculated, and assumptions were explored in scenario analyses. All costs are expressed in 2017 Canadian dollars ($Can). Compared with clobazam and valproate alone, the adjunctive use of Stiripentol is associated with an ICER of $Can151,310. At a willingness-to-pay threshold of $Can50,000, the probability that Stiripentol was the optimal treatment was 5.2%. The cost of Stiripentol would need to be reduced by 61.4% for Stiripentol to be cost effective. From the perspective of the Canadian public healthcare payer, Stiripentol is not cost effective at its current price at a willingness-to-pay threshold of $Can50,000. Funding Stiripentol will be associated with important opportunity costs that bear consideration.
Stephane Auvin - One of the best experts on this subject based on the ideXlab platform.
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Stiripentol exhibits higher anticonvulsant properties in the immature than in the mature rat brain
Epilepsia, 2013Co-Authors: Stephane Auvin, Cecile Lecointe, Nina Dupuis, Beatrice Desnous, Sophie LebonAbstract:Summary Purpose After the first positive experimental data in rodents in the early 1970s demonstrating the anticonvulsant effect of Stiripentol (STP), in vitro studies showed that STP acts directly on γ-aminobutyric acid A (GABAA) receptors. Chloride influx is higher when these receptors contain an α3 subunit, leading to the hypothesis that STP might exhibit higher efficacy in the immature brain. Methods We explored this issue by studying the efficacy of STP in P21 and P75 rats using the pentylenetetrazol model of acute seizures or the lithium-pilocarpine status epilepticus model. P21 and adult rats received vehicle, 150, 250, or 350 mg/kg of STP, i.p., 1 h before evaluating the anticonvulsant. We also studied the blood and brain levels of STP as well as the expression and the messenger RNA (mRNA) levels of the α3 subunit of the GABAA receptors at both ages. Keys Findings STP exhibited anticonvulsant properties in both models at both ages, but STP was more effective in P21 than in P75 rats. This was shown by the significant suppression of seizure or status epilepticus occurrence in P21 with 350 mg/kg STP, whereas the same dose had no significant effect at P75. The blood level, brain level, and blood/brain ratio of STP did not explain these differences between the two age groups. Moreover, the higher anticonvulsant properties in the immature brain were not explained by the mRNA level or protein expression of the GABAA α3 subunit at either age. Significance Stiripentol exhibits higher anticonvulsant properties in the immature than in the mature brain. These findings require further investigation because it might lead to new clinical developments.
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malignant migrating partial seizures of infancy controlled by Stiripentol and clonazepam
Brain & Development, 2013Co-Authors: Dana Merdariu, Catherine Delanoe, Nora Mahfoufi, Vanina Bellavoine, Stephane AuvinAbstract:The syndrome of malignant migrating partial seizures of infancy (MMPSI) is characterized by early onset of multiple seizure types and overall poor prognosis. Seizures are markedly drug resistant and few reports have suggested the efficacy of some antiepileptic drugs. We report one case of MMPSI in which prolonged seizure control is obtained with an association of clonazepam, levetiracetam and Stiripentol, confirming thus the possibility of complete sustained seizure control in this epileptic syndrome. Of more than 60 cases reported to date, ours is the forth in which sustained complete control of seizures was obtained.
