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 par tial seizures and frequently will be added to phenytoin. The objective of t his study was to determine the presence or absence of a pharmacokinetic dru g interaction of levetimcetam with phenytoin. A stable isotope tracer techn ique using deuterium-labeled (D-10) phenytoin and highperformance liquid ch romatography with ultraviolet detection (rather than mass spectrometry dete ction) was employed, Tracer doses of D-10-phenptoin were administered IV be fore and 12 weeks after adding levetiracetam to the regimen of 6 subjects o n phenytoin monotherapy for epilepsy. Blood was collected for 96 hours afte r each infusion. The following pharmacokinetic parameters were determined f or phenytoin: C-max, C-min, C-ave, AUC, CL, t(1/2), VD, and free (nonprotei n bound) fraction. The ra tio and the 90% confidence interval of the ratio of log-transformed mean values for phenytoin pharmacokinetic parameters bef ore (denominator) and after (numerator) adding levetiracetam all fell withi n 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 cha nges in phenytoin pharmacokinetic parameters and that it is not necessary t o change the phenytoin dosing rate when levetiracetam is added to phenytoin .