Abstracts

A sprinkle formulation is now available as an alternative to topiramate (TPM) tablets for the pediatric population. Our aim was to examine the plasma clearance of TPM in the sprinkle and the tablet formulations in a cohort of small ([lt]5years old) children with epilepsy. In an open study, 18 children with epilepsy with a mean age of 2.4 (range 0.3-4.9) years participated. All were on treatment with TPM, nine with the sprinkle and nine with the tablet formulation. In the sprinkle formulation group, TPM was given as monotherapy (n=2) with comedication with nonenzyme inducers (n=4) or enzyme inducers (n=3) and, in the tablet group, TPM was given as monotherapy (n=1) with comedication with nonenzyme inducers (n=5) or enzyme inducers (n=3). A large majority of the children had a generalized epilepsy and the most common seizure types were infantile spasms and tonic seizures. To determine the plasma levels of TPM, serial blood samples were drawn in the morning of the examination day before the intake of TPM as well as after 0.5, 1, 1.5, 2, 4, and 8 h after dosing. All TPM blood sampling was carried out in steady state. The TPM levels were determined by fluorescence polarization immunoassay method (FPIA) and the clearance was calculated by using the software WinNonlin. The clearance of TPM was related to type of formulation, type of comedication and age. The children were divided into age groups; [lt] 2 and 2-4.9 years. The TPM doses (mean [plusmn]SD) were 5.5[plusmn]2.4 mg/kg/day and 4.8[plusmn]1.8 mg/kg/day during treatment with the sprinkle and tablet formulation respectively. The treatment groups did not differ regarding the TPM dosage or age at time of investigation. The plasma clearances (CL/F; mean [plusmn] SD) of TPM were 66.7[plusmn]44 mL/h/kg with the sprinkle formulation treatment and 62.1[plusmn]33 mL/h/kg with the tablets and the difference was not significant. The children on comedication with nonenzyme inducers had a clearance of 41.9[plusmn]10 mL/h/kg and those on enzyme inducers 101.9[plusmn]36 mL/h/kg and the comparison showed highly significant differences (P=0.002). Children [lt]2 years of age had a clearance of 62.6[plusmn]35 mL/h/kg and those [gt]2 years 68.0[plusmn]43 mL/h/kg and the difference was not significant. In children under five years of age, the clearance of TPM sprinkle and tablet formulation did not differ. Within this age group the clearance of TPM was not affected by age but was markedly increased by enzyme-inducing comedication. (Supported by The Margaretahemmet Association)