Stiripentol for the treatment of Dravet syndrome

Figures & data

Figure 1 Structure of stiripentol.

Note: Stiripentol is an aromatic allylic alcohol (4,4-dimethyl-1-[3,4(methylenedioxy)-phenyl]-1-penten-3-ol) that is chemically unrelated to other anticonvulsant drugs.

Table 1 Clinical studies of stiripentol in Dravet syndrome

Study, year	Design	Number of patients	Co-medications	Efficacy (RR)	Safety
Perez et al,^Citation30 1999	Open-label, prospective	20	VPA + CLB	3 months =50%	NA
Chiron et al,^Citation31 2000	RCT versus placebo	41	VPA + CLB	2 months =71%; P<0.0001 versus placebo	AEs in 100% (drowsiness 90%; loss of appetite 33%; weight loss 29%); P<0.0009 versus placebo
Guerrini et al,^Citation32 2002	RCT versus placebo	22	VPA + CLB	2 months =67%; P=0.009 versus placebo	AEs in 90% (drowsiness 58%; loss of appetite 50%; weight loss 17%)
Thanh et al,^Citation12 2002	Open-label, retrospective	46	VPA + CLB	Median 3 years =65%	AEs in 91% (drowsiness 13%; loss of appetite 25%; weight loss 17%)
Inoue et al,^Citation34 2009	Open-label, prospective	23	VPA, ZNS, PB, Br; CLB (50%), CZP; CBZ, PHT	1 month =61% 6 months =48%	AEs in 78% (drowsiness 43%; loss of appetite 35%; irritability 26%)
Vari et al,^Citation35 2010	Open-label, retrospective	6	VPA + CLB	Median 4 years =83%	AEs in 83% (drowsiness 67%)
Wirrell et al,^Citation36 2013	Open-label, retrospective	82	VPA + CLB; VPA, no CLB; No VPA, CLB; No VPA, no CLB	Median 2 years =83% (63%; 57%; 80%; 33%)	AEs in 42% (drowsiness 18%; loss of appetite 8.5%)

Abbreviations: AE, adverse event; Br, bromide; CBZ, carbamazepine; CLB, clobazam; CZP, clonazepam; NA, not available; PB, phenobarbital; PHT, phenytoin; RCT, randomized controlled trial; RR, responder rate; VPA, valproate; ZNS, zonisamide.

Figure 2 Metabolic interactions between CLB and stiripentol by the CYP (cytochrome P450) complex.

Notes: Stiripentol moderately inhibits the formation of N-desmethylclobazam (NCLB) from CLB by CYP2C19 (and, partly, CYP3A4). Stiripentol markedly inhibits the formation of 4′hydroxy-N-desmethylclobazam (OH-NCLB) from norclobazam by CYP2C19.⁴³
Abbreviations: CLB, clobazam; NCLB, norclobazam.

Figure 3 GABAergic anticonvulsant effect of STP in vitro.

Notes: (A) The effect of STP on GABA transmission was studied in the CA3 pyramidal neurons of hippocampal slices of neonatal rats at P8. (B) The patch-clamp method was used. (C) STP increased the decay time constant of the miniature inhibitory postsynaptic currents (mIPSC), which are GABA_A receptor-mediated currents.
Abbreviations: GABA, γ-aminobutyric acid; STP, stiripentol.

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