Hooper W D, Eadie M J, Blakey G E, Lockton J A, Manun'Ebo M
AstraZeneca R & D Charnwood, Bakewell Road, Loughborough, Leicestershire, LE11 5RH, UK.
Br J Clin Pharmacol. 2001 Mar;51(3):249-55. doi: 10.1046/j.1365-2125.2001.00338.x.
To determine whether there is a pharmacokinetic interaction between the antiepileptic drugs remacemide and phenobarbitone.
In a group of 12 healthy adult male volunteers, the single dose and steady-state kinetics of remacemide were each determined twice, once in the absence and once in the presence of phenobarbitone. The effect of 7 days remacemide intake on initial steady-state plasma phenobarbitone concentrations was also investigated.
Apparent remacemide clearance (CL/F) and elimination half-life values were unchanged after 7 days intake of the drug in the absence of phenobarbitone (1.25 +/- 0.32 vs 1.18 +/- 0.22 l kg(-1) h(-1) and 3.29 +/- 0.68 vs 3.62 +/- 0.85 h, respectively). Concomitant administration of remacemide with phenobarbitone resulted in an increase in the estimated CL/F of remacemide (1.25 +/- 0.32 vs 2.09 +/-0.53 l kg-1 h-1), and a decreased remacemide half-life (3.29 +/- 0.68 vs 2.69 +/- 0.33 h). The elimination of the desglycinyl metabolite of remacemide also appeared to be increased after the phenobarbitone intake (half-life 14.72 +/- 2.82 vs 9.61 +/- 5.51 h, AUC 1532 +/- 258 vs 533 +/- 281 ng ml(-1) h). Mean plasma phenobarbitone concentrations rose after 7 days of continuing remacemide intake (12.67 +/- 1.31 vs 13.86 +/- 1.81 microgram ml(-1)).
Phenobarbitone induced the metabolism of remacemide and that of its desglycinyl metabolite. Remacemide did not induce its own metabolism, but had a modest inhibitory effect on the clearance of phenobarbitone.
确定抗癫痫药物瑞玛西胺与苯巴比妥之间是否存在药代动力学相互作用。
在一组12名健康成年男性志愿者中，分别两次测定瑞玛西胺的单剂量和稳态动力学，一次在无苯巴比妥的情况下，一次在有苯巴比妥的情况下。还研究了连续7天服用瑞玛西胺对初始稳态血浆苯巴比妥浓度的影响。
在无苯巴比妥的情况下，服用该药7天后，瑞玛西胺的表观清除率（CL/F）和消除半衰期值未发生变化（分别为1.25±0.32与1.18±0.22 l·kg⁻¹·h⁻¹以及3.29±0.68与3.62±0.85小时）。瑞玛西胺与苯巴比妥同时给药导致瑞玛西胺的估计CL/F增加（1.25±0.32与2.09±0.53 l·kg⁻¹·h⁻¹），且瑞玛西胺半衰期缩短（3.29±0.68与2.69±0.33小时）。服用苯巴比妥后，瑞玛西胺的去甘氨酰代谢物的消除似乎也有所增加（半衰期14.72±2.82与9.61±5.51小时，AUC 1532±258与533±281 ng·ml⁻¹·h）。连续服用瑞玛西胺7天后，平均血浆苯巴比妥浓度升高（12.67±1.31与13.86±1.81 μg·ml⁻¹）。
苯巴比妥诱导瑞玛西胺及其去甘氨酰代谢物的代谢。瑞玛西胺不会诱导自身代谢，但对苯巴比妥的清除有适度抑制作用。
