Multiple‐Dose, Linear, Dose‐Proportional Pharmacokinetics of Retigabine in Healthy Volunteers

  title={Multiple‐Dose, Linear, Dose‐Proportional Pharmacokinetics of Retigabine in Healthy Volunteers},
  author={G{\'e}raldine M. Ferron and Jeffrey Paul and Richard J. Fruncillo and Lyette S Richards and Norbert G Knebel and John Getsy and Steven Troy},
  journal={The Journal of Clinical Pharmacology},
  • G. FerronJ. Paul S. Troy
  • Published 1 February 2002
  • Medicine, Biology
  • The Journal of Clinical Pharmacology
Retigabine, a first‐in‐class selective M‐current potassium channel opener, is a novel antiepileptic compound currently in clinical development. The purpose of this randomized placebo‐controlled study was to assess retigabine oral safety and pharmacokinetics in healthy male volunteers (N = 45). Subjects received one dose on day 1 and doses every 12 hours for the next 14 days. Fixed doses were given to the first four groups (200, 400, 500, and 600 mg per day). Titrated doses were given to group 5… 

Lack of pharmacokinetic interaction between retigabine and phenobarbitone at steady-state in healthy subjects.

No dosage adjustment is likely to be necessary when retigabine and phenobarbitone are coadministered to patients, and no clinically relevant changes were observed in the electrocardiograms, vital signs or laboratory measurements.

Pharmacokinetic interaction between retigabine and lamotrigine in healthy subjects

The induction of LTG clearance due to retigabine was unexpected since RGB did not show enzyme induction in various other drug–drug interaction studies, and RGB and LTG exhibit a modest pharmacokinetic interaction on each other.

Randomized, multicenter, dose-ranging trial of retigabine for partial-onset seizures

Adjunctive therapy with retigabine is well tolerated and reduces the frequency of partial-onset seizures in a dose-dependent manner.

Pharmacokinetics of XEN496, a Novel Pediatric Formulation of Ezogabine, Under Fed and Fasted Conditions: A Phase 1 Trial

The biopharmaceutical performance of XEN496 in this study was as expected for an immediate-release, granular dosage formulation, and generally comparable to that reported for ezogabine tablets.

Randomized, double-blind, placebo-controlled trial of ezogabine (retigabine) in partial epilepsy

This study demonstrates that EZG(RTG) 1,200 mg/day is effective as add-on therapy for reducing seizure frequency in patients with drug-resistant partial-onset seizures.

Lack of effect of ezogabine/retigabine on the pharmacokinetics of digoxin in healthy individuals: results from a drug–drug interaction study

Co-administration of EZG/RTG across the therapeutic range resulted in small, non-dose-dependent and non-clinically relevant increases in digoxin systemic exposure, suggesting that digoxin dose adjustment is not necessary.

Retigabine: in partial seizures.

When used as adjunctive therapy in patients with partial seizures, retigabine 600-1200 mg/day (200-400 mg three times daily) was associated with significant linear dose-dependent reductions in monthly seizure frequency compared with placebo in a large 16-week randomised phase II trial.

Efficacy of Retigabine in Adjunctive Treatment of Partial Onset Seizures in Adults

  • M. Y. Splinter
  • Medicine, Biology
    Journal of central nervous system disease
  • 2013
Retigabine has been shown to have efficacy when used as adjunctive therapy in partial-onset seizures, and has less drug interactions than many other anticonvulsants because it is not metabolized through the P-450 system.



Population Pharmacokinetics of Lamotrigine Adjunctive Therapy in Adults with Epilepsy

Dosing adjustments for lamotrigine in patients receiving concomitant enzyme‐inducing antiepileptic drugs and not valproic acid should not be necessary for age, gender, or the number of concomant enzyme‐ inducing antIEpileptic drugs.

New antiepileptic drugs.

No fewer than eight new antiepileptic drugs (AEDs) with diverse mechanisms of action have been introduced into clinical practice in the 1990s and an attempt has been made to identify ongoing studies and important omissions.

How about the new antiepileptic drugs?

  • B. Wilder
  • Medicine
    The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques
  • 1994
The new AEDs will provide an opportunity to improve the care of epileptic patients, as few controlled clinical trials have been done in patients with absence and myoclonic seizures.

D-23129: a new anticonvulsant with a broad spectrum activity in animal models of epileptic seizures

New antiepileptic drugs.

  • L. Sander
  • Medicine, Psychology
    Epilepsy research. Supplement
  • 1991
New antiepileptic drugs (AEDs) are necessary for people with chronic epilepsy and for improving upon established AEDs as first-line therapy and a guide to dosing in adults and adolescents is given.

In vitro glucuronidation of D-23129, a new anticonvulsant, by human liver microsomes and liver slices.

The metabolic profile of D-23129, a new anticonvulsant agent, was studied in vitro using human liver microsomes and fresh liver slices and phase II conjugation dominated the metabolism producing two distinct N-glucuronides as the primary metabolites.

D-23129: a potent anticonvulsant in the amygdala kindling model of complex partial seizures.

Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels.

It is suggested that activation of KCNQ2/Q3 channels may be responsible for at least some of the anticonvulsant activity of this agent.

Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine.

It is shown that retigabine acts as a KCNQ potassium channel opener, and it is likely that M-current modulation can explain the anticonvulsant actions of retIGabine in animal models of epilepsy.