Pharmacokinetics, Safety, and Tolerability of the New Antiepileptic Drug Carisbamate (RWJ-333369) in Elderly Adults
Abstract number :
3.211;
Submission category :
7. Antiepileptic Drugs
Year :
2007
Submission ID :
7957
Source :
www.aesnet.org
Presentation date :
11/30/2007 12:00:00 AM
Published date :
Nov 29, 2007, 06:00 AM
Authors :
I. Ragueneau-Majlessi1, R. Levy1, B. Solanki2, P. Zannikos3, G. Novak3
Rationale: The disposition of carisbamate (RWJ-333369) immediate release (IR) tablets, a new neuromodulator currently under investigation for epilepsy, was studied in healthy elderly volunteers. Methods: Carisbamate IR was studied in 8 subjects aged 65 to 74 years, 8 subjects aged ≥75 years, and 8 non-elderly healthy adults aged 18 to 55 years (4 men and 4 women per group) in a randomized, double-blind, placebo-controlled, parallel-group, single-center study. In each age group, subjects were randomly assigned to receive carisbamate or placebo with a 3:1 ratio. Carisbamate was administered as a 100-mg oral single dose (day 1), followed by increasing repeated doses of up to 500 mg twice daily (days 5-23). Plasma and urine samples were analyzed following the first dose and at steady-state for carisbamate and its glucuronidated metabolites.Results: Twenty-three of the 24 enrolled subjects completed the study (one subject withdrew consent). After both single and repeated dosing, AUC, Cmax, CL/F, Vd/F, and t1/2 of carisbamate were similar among all age groups. There was also no effect of age on the amount of drug recovered in urine as glucuronidated conjugates. Carisbamate showed moderate binding (40%-43%) to plasma proteins across all age groups. Renal clearance decreased with age, but because of the limited renal elimination of the drug (less than 5%), this decrease had no effect on the total clearance. Treatment with carisbamate was safe and well tolerated. The most commonly reported adverse events were headache, influenza-like illness, and dizziness, with no apparent differences between age groups. All AEs were mild except in one subject, whose influenza-like symptoms were moderate in severity.Conclusions: No apparent differences in pharmacokinetic parameters of carisbamate were observed between elderly and nonelderly subjects after administration of the IR formulation (for both single and multiple dosing). This study confirmed the linearity of carisbamate pharmacokinetics at 250 mg and 500 mg administered twice daily. The drug was generally safe and well tolerated during the study. (Sources of funding: Johnson & Johnson PRDUS, LLC and SK Bio-Pharmaceuticals)
Antiepileptic Drugs