Absence of pharmacokinetic drug interaction of levetiracetam with phenytoin in patients with epilepsy determined by new technique

Levetimcetam has recently been approved as an adjunctive medication for partial seizures and frequently will be added to phenytoin. The objective of this study was to determine the presence or absence of a pharmacokinetic drug interaction of levetimcetam with phenytoin. A stable isotope tracer technique using deuterium-labeled (D-10) phenytoin and highperformance liquid chromatography with ultraviolet detection (rather than mass spectrometry detection) was employed, Tracer doses of D-10-phenptoin were administered IV before and 12 weeks after adding levetiracetam to the regimen of 6 subjects on phenytoin monotherapy for epilepsy. Blood was collected for 96 hours after each infusion. The following pharmacokinetic parameters were determined for phenytoin: C-max, C-min, C-ave, AUC, CL, t(1/2), VD, and free (nonprotein bound) fraction. The ra tio and the 90% confidence interval of the ratio of log-transformed mean values for phenytoin pharmacokinetic parameters before (denominator) and after (numerator) adding levetiracetam all fell within the range of 0.85 to 1.17 (two one-sided test). The authors conclude that the addition of levetiracetam did not bring about clinically important changes in phenytoin pharmacokinetic parameters and that it is not necessary to change the phenytoin dosing rate when levetiracetam is added to phenytoin.