Levy Rene, Ragueneau-Majlessi Isabelle, Solanki Bhavna, Zannikos Peter, Yao Caiping, Novak Gerald
Department of Pharmaceutics, University of Washington, H-272, Health Science Building, Box 357610, Seattle, WA 98195-7610, USA.
Epilepsy Res. 2008 Mar;79(1):22-30. doi: 10.1016/j.eplepsyres.2007.12.013. Epub 2008 Feb 14.
To evaluate the effect of age on the disposition of two different oral formulations of carisbamate (RWJ-333369), a novel neuromodulator under investigation.
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.
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.
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.
评估年龄对新型神经调节剂卡立普胺（RWJ-333369）两种不同口服制剂处置的影响。
在三个年龄组（18 - 55岁、65 - 74岁和≥75岁）的每组8名男性和8名女性中（N = 48）研究卡立普胺的处置情况。在一项随机、双盲、安慰剂对照、平行组、单中心研究中，受试者接受单次（100mg速释[IR]片或250mg控释[CR]片）或重复给药（高达500mg IR每日两次或1250mg CR每日一次）的卡立普胺。
单次或重复给予IR制剂后，两个老年组和非老年组之间未观察到明显差异。单次给予CR制剂后，两个老年年龄组的暴露量高于非老年受试者，但重复给药后，在所有测试剂量下差异均减小。年龄对卡立普胺的血浆蛋白结合无影响。两种制剂的肾清除率均随年龄降低，但由于其肾排泄有限，这种降低对药物的总清除率无影响。
年龄对卡立普胺IR制剂的药代动力学无影响。单次给予CR卡立普胺后观察到的小影响在重复给药后减弱。该药物总体安全且耐受性良好。
