EFFECT OF STIRIPENTOL ON CARBAMAZEPINE PLASMA-CONCENTRATION AND METABOLISM IN EPILEPTIC CHILDREN

Objective: To study the relationship between the plasma concentration of stiripentol (STP), a new antiepileptic drug, and its inhibitory eff ect on the formation of carbamazepine epoxide (CBZE) in epileptic chil dren treated with carbamazepine (CBZ) either alone or in combination w ith another antiepileptic drug. Methods: Minimum plasma concentration of antiepileptic drugs was measured before initiation of STP therapy ( day 0) and oil days 28 (STP 60 mg . kg(-1) . day(-1)) and 54 (STP 90 m g . kg(-1) day(-1)) by HPLC, Results: The CBZE/CBZ plasma concentratio n ratio decreased exponentially with increasing minimum plasma STP con centration (r = 0.80), The asymptote of the curve allowed the calculat ion of the minimum plasma STP concentration required to obtain the max imum inhibitory effect, i,e. 6.7 mg . l(-1). Conclusion: The inhibitor y effect of STP on CBZ metabolism expressed as the CBZE/CBZ plasma con centration ratio is dependent on STP plasma concentration, with a maxi mum 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 the rapy, 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 concent ration.