Influence of domperidone on pharmacokinetics, safety and tolerability of the dopamine agonist rotigotine
Influence of domperidone on pharmacokinetics, safety and tolerability of the dopamine agonist rotigotine
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DOI：
10.1111/j.1365-2125.2008.03334.x
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发表时间：
2009-02-01
影响因子：
3.4
通讯作者：
Horstmann, Rolf
中科院分区：
文献类型：
--
作者：
Braun, Marina;Cawello, Willi;Horstmann, Rolf
罗替戈汀透皮贴剂是一种新的非麦角碱多巴胺激动剂，开发用于治疗帕金森病和不宁腿www.example.com dot多巴胺激动剂的外周多巴胺能副作用，如恶心和呕吐，可以通过止吐剂多潘立酮预防。syndrome.center（平均年龄30.3岁）参加了一项随机、双向交叉临床试验。治疗A包括透皮罗替戈汀贴剂（2 mg（24 h）（-1），10 cm（2），总药物含量4.5 mg），每日应用4天，同时口服多潘立酮（10 mg t.i.d.）连续5d对于治疗B，受试者仅接受透皮罗替戈汀治疗（每天一次，持续4天）。主要稳态药代动力学参数（C（max，ss）和AUC（（0 - 24），ss））与多潘立酮联合给药或不联合给药相似。几何均值比接近1，相应的90%置信区间在生物等效性的验收范围内（0.8，1.25）：C（max，ss）0.96（0.86，1.08）和AUC（（0 - 24），ss）0.97（0.87，1.08）。t（max，ss）、t（1/2）、重复贴剂贴敷后第4/5天计算的次要参数（C（min，ss）、C（ave，ss）、AUC（（0-tz）和未结合罗替戈汀及其代谢物的肾脏消除在合并和不合并多潘立酮的情况下也相似。当多潘立酮与罗替戈汀同时给药时，没有观察到描述罗替戈汀全身暴露和肾脏消除的药代动力学参数的变化。药代动力学相互作用的缺乏表明罗替戈汀透皮贴剂的剂量调整与多潘立酮的合并使用是不必要的。
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECTcenter dot Rotigotine transdermal patch is a new non-ergolinic dopamine agonist developed for the treatment of Parkinson's disease and restless legs syndrome.center dot Peripheral dopaminergic side-effects of dopamine agonists such as nausea and vomiting can be prevented by the antiemetic agent domperidone.WHAT THIS STUDY ADDScenter dot The study results show no evidence for an interaction of domperidone on bioavailability and steady-state pharmacokinetics of transdermal rotigotine.center dot Co-administration of domperidone and rotigotine does not require dose adjustments for rotigotine transdermal patch.To evaluate the influence of the antiemetic agent domperidone on steady-state pharmacokinetics, safety and tolerability of multiple-dose treatment of the transdermally applied non-ergolinic dopamine agonist rotigotine.Sixteen healthy male subjects (mean age 30.3 years) participated in a randomized, two-way crossover clinical trial. Treatment A consisted of transdermal rotigotine patch (2 mg (24 h)(-1), 10 cm(2), total drug content 4.5 mg) applied daily for 4 days, and concomitant oral domperidone (10 mg t.i.d.) for 5 days. For treatment B, subjects received only transdermal rotigotine treatment (daily for 4 days). Pharmacokinetic variables describing systemic exposure and renal elimination of rotigotine and metabolites, and safety and tolerability of the treatment were assessed.The primary steady-state pharmacokinetic parameters (C(max,ss) and AUC((0-24),ss)) were similar with or without co-administration of domperidone. Geometric mean ratios were close to 1 and respective 90% confidence intervals were within the acceptance range of bioequivalence (0.8, 1.25): C(max,ss) 0.96 (0.86, 1.08) and AUC((0-24),ss) 0.97 (0.87, 1.08). t(max,ss), t(1/2), secondary parameters calculated on days 4/5 after repeated patch application (C(min,ss), C(ave,ss), AUC((0-tz))) and renal elimination for unconjugated rotigotine and its metabolites were also similar with and without comedication of domperidone. A reduction in the dopaminergic side-effect nausea was seen with domperidone comedication.No changes of pharmacokinetic parameters describing systemic exposure and renal elimination of rotigotine were observed when domperidone was administered concomitantly with rotigotine. The lack of pharmacokinetic interactions indicates that a dose adjustment of rotigotine transdermal patch is not necessary with concomitant use of domperidone.