Eligard®:: Pharmacokinetics, effect on testosterone and PSA levels and tolerability
Eligard®:: Pharmacokinetics, effect on testosterone and PSA levels and tolerability
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DOI：
10.1016/j.eursup.2005.04.001
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发表时间：
2005-07-01
影响因子：
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通讯作者：
Berges, R
中科院分区：
文献类型：
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作者：
Berges, R
促黄体生成素释放激素(LHRH)激动剂(如亮丙瑞林)已成为晚期和转移性前列腺癌治疗的主要药物。LHRH激动剂治疗也已成为早期前列腺癌治疗的一部分，作为根治性治疗的新辅助和辅助治疗。早期的治疗包括每天注射合成的LHRH类似物(如亮丙瑞林、Goerelin)，但近年来出现了1、3或4个月注射的仓库配方的发展。这些仓库配方对目前LHRH激动剂的广泛使用做出了相当大的贡献，并提高了患者对治疗的依从性。不幸的是，有了这些配方，目前对睾酮最佳控制的实现被高估了，这种最佳控制被定义为适当的阉割水平和低水平的突破，以及对慢性急性反应的最佳控制。为了实现对睾酮的最佳控制，已经开发了一种新的亮丙瑞林仓库配方Eligard(R)，其中包含一种新的给药系统(Arigel(R))，它与旧系统相比具有潜在的优势。Eligard(R)具有良好的药代动力学特征，以一致和稳定的方式提供的LHRH激动剂数量是欧洲联盟(EU)其他可用仓库制剂的两倍。结果，睾丸激素水平得到了更好的抑制，与其他输送系统不同，Eligard(R)达到了睾丸切除后的睾丸激素水平，到目前为止还没有表现出逃逸反应。此外，临床试验表明，Eligard(R)会产生轻微的潮热症状。Eligard(R)体积小，用非常短的针头皮下注射，减少了注射部位的不适。与皮下注射相关的主要不良反应轻微且持续时间短，包括刺激、皮肤变色和红斑。结论是，Eligard(R)由一种新型递送系统组成，与其他现有的仓库制剂相比，具有更好的药代动力学曲线，导致可靠和持续的睾酮抑制，并具有良好的副作用曲线。(C)2005年，爱思唯尔出版。
Luteinising hormone releasing hormone (LHRH) agonists (e.g. leuprolide) have been the mainstay of advanced and metastatic prostate cancer treatment. LHRH agonist treatment has also become part of the treatment of early prostate cancer as neoadjuvant and adjuvant treatment to radical therapy.Early therapies consisted of daily injections of synthetic LHRH analogues (e.g. leuprolide, goserelin), but recent years have seen the development of depot formulations with 1, 3 or 4-monthly injections. These depot formulations have contributed considerably to the current widespread use of LHRH agonists, and have improved the patients' adherence to treatment. Unfortunately, with these formulations the achievement of optimal control of testosterone defined as appropriate castration levels and low levels of breakthroughs, as well as acute-on-chronic responses, is currently overestimated.In order to achieve the optimal control of testosterone, a new depot formulation of leuprolide, Eligard (R), has been developed, which contains a novel delivery system (Atrigel (R)) with potential advantages over the older systems. Eligard (R) allows for a favourable pharmacokinetic profile, delivering a twofold higher quantity of LHRH agonist than seen with other available depot preparations in the European Union (EU), in a consistent and stable manner. As a result, testosterone levels are better suppressed and, unlike other delivery systems, Eligard (R) achieves levels of testosterone as seen with orchiectomy and has, to date, shown no escape responses. In addition, clinical trials have shown that Eligard (R) produces mild episodes of hot flushes.Eligard (R) has a small volume which is administered subcutaneously with a very short needle, reducing injection site discomfort. Main adverse events associated with subcutaneous injection are mild and of short duration, comprising irritation, skin discolouration and erythema.It is concluded that Eligard (R), consisting of a novel delivery system with an improved pharmacokinetic profile compared with other existing depot formulations, leads to reliable and sustained testosterone suppression with a favourable side effect profile. (c) 2005 Published by Elsevier B.V.