Effect of stiripentol on carbamazepine plasma concentration and metabolism in epileptic children

Abstract

Objective: To study the relationship between the plasma concentration of stiripentol (STP), a new antiepileptic drug, and its inhibitory effect on the formation of carbamazepine epoxide (CBZE) in epileptic children treated with carbamazepine (CBZ) either alone or in combination with another antiepileptic drug.

Methods:

Minimum plasma concentration of antiepileptic drugs was measured before initiation of STP therapy (day 0) and on days 28 (STP 60 mg⋅kg⁻¹⋅day⁻¹) and 84 (STP 90 mg⋅kg⁻¹⋅day⁻¹) by HPLC.

Results:

The CBZE/CBZ plasma concentration ratio decreased exponentially with increasing minimum plasma STP concentration (r = 0.80). The asymptote of the curve allowed the calculation of the minimum plasma STP concentration required to obtain the maximum inhibitory effect, i.e. 6.7 mg⋅l⁻¹.

Conclusion:

The inhibitory effect of STP on CBZ metabolism expressed as the CBZE/CBZ plasma concentration ratio is dependent on STP plasma concentration, with a maximum effect at an average of 7 mg⋅l⁻¹. The present data suggest that in order to evaluate the anticonvulsant efficacy of STP as add-on therapy, the minimum plasma STP concentration should be maintained above 7 mg⋅l⁻¹ and the dosage of CBZ should simultaneously be decreased in steps by more than 50% to minimize the change in CBZ plasma concentration.