Felbamate: Therapeutic range and other kinetic information

Abstract

A retrospective study was performed to identify the therapeutic range and pharmacokinetic parameters of felbamate (FBM). Data from 104 patients visits were analyzed. FBM was the sole agent in 40%. Dose-related side effects were graded numerically, and seizure experience was coded qualitatively. For 76 visits, seizure control was better than that observed at the previous visit. The FBM therapeutic window was 50–110 mg/L. Doeses required to achieve these levels were 50–55 mg/kg/day. FBM clearance in monotherapy was 0.67 L/kg/day, with a corresponding half-life (+1/2) of 24 h. FBM clearance increased when carbamazepine (CBZ) was combined with FBM, as evidenced by a decrement in FBM +1/2 to 15 h (61% of the FBM +1/2 in monotherapy). No appreciable changes in FBM clearance were demonstrated for comedication with phenytoin (PHT) or lamotrigine (LTG). A slight decrease in clearance was apparent when FBM was combined with valprate (VPA). We identified an interaction between FBM and gabapentin (GBP) in which the elimination of FBM was strikingly reduced, corresponding to a prolonged +1/2 of 35 h (146% of baseline). No idiosyncratic side effects were noted. A new concept, “response/toxicity rario”, is introduced to improve clinicians' use of the therapeutic range.