Stiripentol in Atypical Absence Seizures in Children: An Open Trial

Abstract

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.

Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications

“…e Drug shows zero-order elimination kinetics. f References for reference ranges: felbamate [42,43], gabapentin [44], lacosamide [45], lamotrigine [46], levetiracetam [47], oxcarbazepine (10-hydroxycarbazepine metabolite) [48], pregabalin [2], stiripentol [49], tiagabine [50], topiramate [51], vigabatrin [23], zonisamide [52]. …”

“…Stiripentol is also highly (>99%) protein bound which likely limits clearance of this drug by hemodialysis procedures [19]. The reference range for stiripentol is not well-defined but serum concentrations of 4–22 mg/L correlate with control of absence seizures in children [49]. …”

Stiripentol: Efficacy and Tolerability in Children with Epilepsy

“…In adults, STP has proven to be efficient as an add-on in refractory partial epilepsy (4,5) and refractory absences ( 17,18) rather than in other types of generalized epilepsy. In children, the studies are more recent and concern small series (8,(19)(20)(21), but the metabolism of the drug has been widely described in the pediatric population (22). The combination of STP and CBZ might be useful in partial epilepsy (5,15,16).…”

Therapeutic Drug Monitoring of Antiepileptic Medications

“…Table 1 summarizes the pharmacokinetic properties of the AEMs, while Table 2 presents a summary of the justifications of TDM for the AEMs. References for reference ranges used in Table 1 are as follows: carbamazepine, clonazepam, phenobarbital, phenytoin, primodone, valproic acid (Hardman et al, 1996), felbamate (Faught et al, 1993;Sachdeo et al, 1992), gabapentin (Lindberger et al, 2003), lacosamide (Kellinghaus, 2009), lamotrigine (Bartoli et al, 1997) (Friis et al, 1993), pregabalin (Patsalos et al, 2008), stiripentol (Farwell et al, 1993), tiagabine (Uthman et al, 1998), topiramate , vigabatrin (Patsalos, 1999), and zonisamide (Glauser & Pippenger, 2000;Mimaki, 1998).…”

“…Stiripentol is also highly (>99%) protein bound and prone to drug interactions that can alter the free fraction (Lacerda et al, 2006). A well-defined reference range for stiripentol has not been established, although one study showed that serum concentrations of 4-22 mg/L correlate with control of absence seizures in children (Farwell et al, 1993). The complex pharmacokinetics of stiripentol (extensive hepatic metabolism, high binding to plasma protein, and saturation kinetics) resemble that of phenytoin (Luszczki, 2009).…”