Lack of Pharmacokinetic Interaction Between Retigabine and Lamotrigine
Abstract number :
2.086
Submission category :
Year :
2000
Submission ID :
2468
Source :
www.aesnet.org
Presentation date :
12/2/2000 12:00:00 AM
Published date :
Dec 1, 2000, 06:00 AM
Authors :
Geraldine M Ferron, Jeffrey Paul, Lyette S Richards, Norbert Knebel, John A Getsy, Steven M Troy, Wyeth-Ayerst Research, Radnor, PA; Asta Medical, Frankfurt, Germany.
RATIONALE: Lamotrigine and retigabine are antiepileptic compounds, which may be coadministered and are metabolized by similar enzymes. Thus, this study was performed to evaluate the effect of multiple oral doses of retigabine or lamotrigine on the pharmacokinetics of a single dose of lamotrigine or retigabine, respectively. METHODS: Two groups of healthy male volunteers (n=15) were studied. Group A received 200 mg retigabine on day 1, 25 mg of lamotrigine on days 3-8, and 200 mg retigabine on day 7. Group B received 200 mg lamotrigine on day 1, 200 mg retigabine BID on days 6-8, 250 mg retigabine BID on days 9-11, 300 mg retigabine BID on days 12-20, and 200 mg lamotrigine on day 17. Serial blood samples were collected in order to measure concentrations of retigabine and lamotrigine. Pharmacokinetic parameters were compared between treatments. Safety was monitored throughout the study. RESULTS: After administration of a single 200-mg dose of retigabine alone, retigabine was rapidly absorbed and eliminated following first-order processes with a mean terminal half-life of 6.3 hours and an apparent clearance of 0.69 L/hr/kg. The pharmacokinetics of retigabine were not altered under steady-state concentrations of lamotrigine. After administration of a single 200-mg dose of lamotrigine alone, mean lamotrigine pharmacokinetics were characterized by moderately rapid absorption, a terminal half-life of 37 hours, and an apparent oral clearance of 0.028 L/hr/kg. After the administration of lamotrigine under steady-state concentrations of retigabine, lamotrigine clearance slightly increased and was accompanied by a slight decrease in the terminal half-life, but these changes were not statistically significant. All treatments were well tolerated and no serious adverse events were reported. CONCLUSIONS: This study indicated a lack of significant pharmacokinetic interaction between retigabine and lamotrigine at the studied doses. Combination treatments were well tolerated suggesting that no dosage adjustments are needed under coadministration of lamotrigine and retigabine.