Pharmacokinetics, safety, and tolerability of the new antiepileptic carisbamate in the elderly.
OBJECTIVE
To evaluate the effect of age on the disposition of two different oral formulations of carisbamate (RWJ-333369), a novel neuromodulator under investigation.


METHODS
The disposition of carisbamate was studied in eight men and eight women in each of the three age groups: 18-55, 65-74, and >or= 75 years (N=48). Subjects received single (100mg immediate-release [IR] tablets or 250 mg controlled-release [CR] tablets) or repeated administration (up to 500 mg IR BID or 1250 mg CR QD) of carisbamate in a randomized, double-blind, placebo-controlled, parallel-group, single-center study.


RESULTS
After either single or repeated IR administration, no apparent differences were observed between the two elderly and the non-elderly groups. Following single-dose CR administration, the two elderly age groups had higher exposure compared with non-elderly subjects, but the difference decreased for all doses tested after repeated administration. There was no effect of age on plasma protein binding of carisbamate. Renal clearance decreased with age for both formulations, but this decrease had no effect on the total clearance of the drug because of its limited renal elimination.


CONCLUSIONS
Age had no effect on pharmacokinetics of carisbamate IR formulation. The small effect observed after single-dose CR carisbamate diminished after repeated dosing. The drug was generally safe and well tolerated.
Levy
Rene
R
Department of Pharmaceutics, University of Washington, H-272, Health Science Building, Box 357610, Seattle, WA 98195-7610, USA. rhlevy@u.washington.edu
Ragueneau-Majlessi
Isabelle
I
Solanki
Bhavna
B
Zannikos
Peter
P
Yao
Caiping
C
Novak
Gerald
G
D000284:Administration, Oral; D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000187:drug effects*; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002219:Carbamates / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
D000927:Anticonvulsants; D002219:Carbamates; C518914:S-2-O-carbamoyl-1-o-chlorophenyl-ethanol