Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.
Prog Neuropsychopharmacol Biol Psychiatry. 2009 Nov 13;33(8):1526-32. doi: 10.1016/j.pnpbp.2009.08.014. Epub 2009 Sep 4.
To evaluate the potential of pharmacodynamic and pharmacokinetic interactions of a concomitantly administered monoamine oxidase (MAO) type B inhibitor rasagiline and a selective serotonin reuptake inhibitor (SSRI) escitalopram.
Twelve healthy male volunteers received a 10-day regimen of rasagiline 1mg daily, followed by concomitant rasagiline 1mg and escitalopram 10mg daily for 7 days.
We found that the drug combination was generally well tolerated, and there were no signs of central nervous system hyperexcitation or changes in the subjects' vital signs. The reported adverse effects were mainly mild or moderate, and typical for SSRIs. The MAO-A-dependent catecholamine metabolite DHPG levels did not change significantly during the study suggesting that rasagiline's MAO-B selectivity was preserved. The plasma monoamine concentrations indicated no subclinical signs of interaction. As expected, the whole blood serotonin was significantly reduced by escitalopram but unaffected by rasagiline. Rasagiline AUC was increased by 42% (p<0.0001) and the weight-adjusted apparent oral clearance was reduced by 35% (p=0.0009) after 7 days' concomitant escitalopram treatment. Escitalopram reduced the ratio of the AUC values of the main metabolite 1-aminoindan and rasagiline by about 23% (p=0.0079). There were no significant changes in the elimination half-life, t(max) and C(max) of rasagiline.
These results suggest good tolerability of concomitant administration of rasagiline and escitalopram. However, other medications, diseases and aging may change the individual drug response and tolerability of concomitant rasagiline and escitalopram, e.g. in Parkinsonian patients, and thus careful monitoring is recommended when combining rasagiline and escitalopram.
评估同时给予单胺氧化酶（MAO）B 抑制剂雷沙吉兰和选择性 5-羟色胺再摄取抑制剂（SSRI）依地普仑的药效动力学和药代动力学相互作用的潜力。
12 名健康男性志愿者接受雷沙吉兰 1mg 每日治疗 10 天，随后同时给予雷沙吉兰 1mg 和依地普仑 10mg 每日治疗 7 天。
我们发现该药物联合治疗通常耐受性良好，且受试对象的生命体征无中枢神经系统兴奋或变化迹象。报告的不良反应主要为轻度或中度，且为 SSRI 的典型不良反应。研究期间，MAO-A 依赖性儿茶酚胺代谢物 DHPG 水平无明显变化，表明雷沙吉兰的 MAO-B 选择性得以保留。血浆单胺浓度表明无亚临床相互作用迹象。依地普仑可显著降低全血 5-羟色胺，而雷沙吉兰无影响，这符合预期。与单独使用雷沙吉兰相比，依地普仑合用 7 天后雷沙吉兰 AUC 增加 42%（p<0.0001），体重校正的表观口服清除率降低 35%（p=0.0009）。依地普仑使雷沙吉兰主代谢物 1-氨基茚满的 AUC 比值降低约 23%（p=0.0079）。雷沙吉兰的消除半衰期、t(max)和 C(max)无显著变化。
这些结果表明雷沙吉兰和依地普仑同时给药具有良好的耐受性。然而，其他药物、疾病和衰老可能会改变个体对同时使用雷沙吉兰和依地普仑的药物反应和耐受性，例如帕金森病患者，因此建议在合并使用雷沙吉兰和依地普仑时密切监测。
