• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of opioid management >Does tapentadol affect sex hormone concentrations differently from morphine and oxycodone? An initial assessment and possible implications for opioid-induced androgen deficiency
【24h】

Does tapentadol affect sex hormone concentrations differently from morphine and oxycodone? An initial assessment and possible implications for opioid-induced androgen deficiency

机译：他喷他多对性激素浓度的影响不同于吗啡和羟考酮吗？阿片类药物引起的雄激素缺乏症的初步评估及其可能的意义

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Objectives: Opioid-induced androgen deficiency (OPIAD) affects patients treated with opioid analgesics. The norepinephrine reuptake inhibitor (NRI) and μ-opioid receptor (MOR) agonist activities of tapentadol may result in tapentadol having less effect on serum androgen concentrations than analgesics acting through the MOR alone, such as morphine and oxycodone. The objectives of this publication are to 1) evaluate the effects of tapentadol (NUCYNTA and NUCYNTA extended release [ER]) on sex hormone concentrations in healthy male volunteers (vs placebo and morphine) and patients with osteoarthritis (vs placebo and oxycodone), and 2) present a mechanistic hypothesis explaining how the combined MOR agonist and NRI activities of tapentadol may result in less impact on androgen concentrations. Methods: Three clinical studies were conducted: study 1 (single-dose comparison study vs morphine in healthy volunteers), study 2 (single-dose-escalation study in healthy volunteers without an active comparator), and study 3 (multiple-dose study vs oxycodone in patients with osteoarthritis). Studies 1 and 2 were conducted at medical research centers in Germany and the United Kingdom; study 3 was conducted at primary and secondary care centers and medical research centers in the United States. All three studies were randomized, double blind, and placebo con-trolled. Concentrations of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH; study 3 only) were evaluated at 6 and 24 hours postdose in studies 1 and 2, respectively, and at varying time points postdose in study 3. Results: In study 1, mean serum total testosterone concentrations in healthy male volunteers were similar at baseline for all treatment periods; 6 hours after dosing, mean concentrations were comparable between placebo (8.6 nmol/L) and tapentadol immediate release (IR; 43 mg, 8.8 nmol/L; 86 mg, 9.3 nmol/L), but were lower following administration of morphine IR 30 mg (5.4 nmol/L). In study 2, there were no or minimal changes in testosterone in the therapeutic dose range with tapentadol IR (75-100 mg), and there was a modest decrease that appeared to level off in the supratherapeutic range (125-175 mg); mean testosterone and LH concentrations with all doses remained within normal ranges (testosterone, 4.56-28.2 nmol/L; LH, 2.9-4.6 U/L). In study 3, the decrease in the mean [standard deviation] testosterone concentration from baseline to endpoint for male patients receiving tapentadol ER (100 mg, -1.9 [0.71] nmol/L; 200 mg, -2.1 [0.93] nmol/L) was numerically smaller compared to oxycodone CR (20 mg, -2.7 [0.931 nmol/L), but higher compared to placebo (-0.3 [1.62] nmol/L). Conclusions: These results suggest that tapentadol, which has combined MOR and NRI activities, may have a lower impact on sex hormone concentrations than pure opioid analgesics, such as morphine or oxycodone. The data and mechanistic rationale presented herein provide a justification for conducting additional hypothesis testing studies, and are not intended to be used as a basis for clinical decision making. Future studies may help elucidate whether the observed trends are clinically significant and would translate into a reduced incidence of OPIAD.
机译：目的：阿片类药物引起的雄激素缺乏症（OPIAD）影响使用阿片类镇痛药治疗的患者。他喷他多的去甲肾上腺素再摄取抑制剂（NRI）和μ阿片受体（MOR）激动剂活性可能导致他喷他多对血清雄激素浓度的影响比仅通过MOR的镇痛药（例如吗啡和羟考酮）少。该出版物的目的是：1）评价他喷他多（NUCYNTA和NUCYNTA缓释[ER]）对健康男性志愿者（相对于安慰剂和吗啡）和骨关节炎患者（相对于安慰剂和羟考酮）中性激素浓度的影响，以及2）给出了一个机械学假说，解释了他喷他多的MOR激动剂和NRI组合活性如何对雄激​​素浓度产生较小的影响。方法：进行了三项临床研究：研究1（健康志愿者中的单剂量比较研究与吗啡），研究2（没有活跃比较者的健康志愿者中的单剂量递增研究）和研究3（多剂量研究与多药研究）羟考酮治疗骨关节炎患者）。研究1和2在德国和英国的医学研究中心进行;研究3是在美国的初级和二级保健中心以及医学研究中心进行的。所有这三项研究均为随机，双盲和安慰剂对照。在研究1和2的给药后6和24小时，以及在研究3的给药后的不同时间点，分别评估睾丸激素，黄体生成素（LH）和促卵泡激素（FSH;仅研究3）的浓度。结果：在研究1中，健康男性志愿者的平均血清总睾丸激素浓度在所有治疗期间的基线水平均相似。给药后6小时，安慰剂（8.6 nmol / L）和他喷他多即刻释放（IR; 43 mg，8.8 nmol / L; 86 mg，9.3 nmol / L）的平均浓度相当，但在服用吗啡IR 30后较低毫克（5.4 nmol / L）。在研究2中，在使用他喷他多IR（75-100 mg）的治疗剂量范围内，睾丸激素没有变化或变化很小，而在治疗上剂量范围内（125-175 mg）则出现了适度的下降，趋于平稳。所有剂量的平均睾丸激素和LH浓度均保持在正常范围内（睾丸激素为4.56-28.2 nmol / L; LH为2.9-4.6 U / L）。在研究3中，接受他喷他多ER的男性患者从基线到终点的平均[标准偏差]睾丸激素浓度降低（100 mg，-1.9 [0.71] nmol / L; 200 mg，-2.1 [0.93] nmol / L）与羟考酮CR（20 mg，-2.7 [0.931 nmol / L]）相比在数值上更小，但与安慰剂（-0.3 [1.62] nmol / L）相比更高。结论：这些结果表明，结合了MOR和NRI活性的他喷他多对性激素浓度的影响可能比纯阿片类镇痛药（例如吗啡或羟考酮）低。本文提供的数据和机制原理为进行额外的假设检验研究提供了依据，并且无意用作临床决策的基础。未来的研究可能有助于阐明观察到的趋势是否在临床上具有重要意义，并会降低OPIAD的发生率。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号