Stiripentol.
Stiripentol (STP) is a new antiepileptic compound produced by Biocodex. It is not structurally related to any of the other currently marketed antiepileptic products as it belongs to the group of aromatic allylic alcohols. It has recently been proved to increase GABAergic transmission in experimental models. It has been studied and used in France and Canada for > 10 years, but its clinical development was delayed due to the inhibitory effect of STP on hepatic cytochrome P450 (CYP). Clinical studies were based on the fact that STP also acts as an inhibitor of CYP3A4, CYP1A2 and CYP2C19 in vivo in epileptic patients. Although the studies in adult patients were disappointing, the trials conducted in paediatric populations demonstrated a specific efficacy of STP in a severe form of early childhood epilepsy, Dravet syndrome (severe myoclonic epilepsy in infancy), when combined with valproate and clobazam. Based on these results, STP was granted orphan drug status in the European Union for the treatment of Dravet syndrome. The French experience in compassionate use suggests that STP might also be of benefit when combined with carbamazepine in paediatric patients with pharmacoresistant partial epilepsy. Nevertheless, two controlled adjunctive-therapy trials were recently completed in paediatric populations with epilepsy. The interactions of STP with a large number of drugs need to be carefully taken into account by adjusting the doses of the combined antiepileptic drugs in order to improve the tolerability of the therapeutic association.
Chiron
Catherine
C
Service de Neurologie et Metabolisme Hôpital Necker, INSERM U663, 149 rue de Sèvres, 75015 Paris, France. catherine.chiron@nck.aphp.fr
D000927:Anticonvulsants / Q000737:chemistry / Q000627:therapeutic use*; D004148:Dioxolanes / Q000737:chemistry / Q000627:therapeutic use*; D004347:Drug Interactions / Q000502:physiology; D015507:Drugs, Investigational / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D012640:Seizures / Q000188:drug therapy / Q000378:metabolism
D000927:Anticonvulsants; D004148:Dioxolanes; D015507:Drugs, Investigational; C021092:stiripentol