Pregabalin effect on steady-state pharmacokinetics of carbamazepine, lamotrigine, phenobarbital, phenytoin, topiramate, valproate, and tiagabine.
Author(s): Bockbrader HN, Burger P, Knapp L
Affiliation(s): Neurosciences, Clinical Pharmacology, Pfizer Global Research & Development, New London, Connecticut 06320, USA. Howard.Bockbrader@pfizer.com
Publication date & source: 2011-02, Epilepsia., 52(2):405-9. Epub 2010 Nov 3.
Publication type: Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
By reducing neuronal excitability through selective binding to the alpha(2)delta subunit of voltage-dependent calcium channels, pregabalin effectively treats epilepsy, chronic pain, and anxiety disorders. To evaluate if pregabalin coadministration affects pharmacokinetics of other antiepileptic drugs, population pharmacokinetic analyses using NONMEM software were performed on data from three epilepsy trials involving seven antiepileptic drugs with pregabalin as add-on therapy. Results demonstrated that pregabalin did not alter the steady-state plasma concentrations of carbamazepine, lamotrigine, phenobarbital, phenytoin, tiagabine, topiramate, and valproate. Furthermore, the small percent change in the population estimate of antiepileptic drug plasma clearance values (-2% to +7%) suggests that pregabalin coadministration exerted no significant effect on the pharmacokinetics of these antiepileptic drugs, with the possible exception of tiagabine (+34.9%). These findings are in agreement with those of previously published reports. A further clarification study is necessary for tiagabine. In conclusion, it appears that pregabalin can be coadministered with other antiepileptic drugs without concern for significantly altering their pharmacokinetic profiles. Wiley Periodicals, Inc. (c) 2010 International League Against Epilepsy.