Adolescent Clinical Development of Ezogabine/Retigabine as Adjunctive Therapy for Partial-Onset Seizures: Pharmacokinetics and Tolerability.

To explore the pharmacokinetic (PK) profile and safety of ezogabine (EZG)/retigabine (RTG) as adjunctive therapy for uncontrolled partial-onset seizures (POS) in adolescents. In this multiple-dose study (NCT01494584), adolescents with POS received EZG/RTG immediate-release tablets three times daily (TID) as adjunctive therapy to 1 to 3 concurrent antiepileptic drugs. The study comprised a screening phase, and a 5- to 8-week treatment phase starting with 100 mg TID up-titrated once weekly by ≤50 mg TID to a maximum dosage of 300 mg TID.

Investigation of the Brain Biodistribution of the Lipoprotein-Associated Phospholipase A (Lp-PLA) Inhibitor [F]GSK2647544 in Healthy Male Subjects.

Purpose: GSK2647544 is a potent and specific inhibitor of lipoprotein-associated phospholipase A (Lp-PLA), which was in development as a potential treatment for Alzheimer's disease (AD). In order to refine therapeutic dose predictions and confirm brain penetration, a radiolabelled form of the inhibitor, [F]GSK2647544, was manufactured for use in a positron emission tomography (PET) biodistribution study.

Procedures: [F]GSK2647544 was produced using a novel, copper iodide (Cu(I)) mediated, [F]trifluoromethylation methodology.

Effect of hemodialysis on pharmacokinetics of ezogabine/retigabine and its N-acetyl metabolite in patients with end stage renal disease.

Ezogabine (EZG)/retigabine (RTG) and its metabolites are mainly eliminated renally. This Phase I study assessed the effect of hemodialysis on the pharmacokinetics of EZG/RTG and its N-acetyl metabolite (NAMR) in patients with end-stage renal disease; tolerability of EZG/RTG was a secondary endpoint. Patients (N=8) received EZG/RTG 100 mg orally 4 hours before (Period 1) or following (Period 2) dialysis.

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

Introduction: The potential for ezogabine/retigabine (EZG/RTG) and its N-acetyl metabolite (NAMR) to inhibit the transporter protein P-glycoprotein-(P-gp)-mediated digoxin transport was tested in vitro. EZG/RTG did not inhibit P-gp. However, NAMR inhibited P-gp in a concentration-dependent manner.

The effect of ezogabine on the pharmacokinetics of an oral contraceptive agent.

Objectives: Ezogabine (EZG) is a potassium-channel opener that has been approved as adjunctive treatment for partial-onset seizures in adults with epilepsy. This Phase I clinical study evaluated the pharmacokinetics (PK), safety, and tolerability of coadministration of EZG and a combined oral contraceptive (OC).

Methods: An open-label drug-interaction study was conducted in healthy, female volunteers aged 18 - 55 years with regular menstrual cycles.