Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, Rome, Italy; Drug Addiction and Clinical Pharmacology Unit, University Hospital Umberto I, Sapienza University of Rome, Rome, Italy.
Department of Biology, University of Rome 'Tor Vergata', Rome, Italy.
Pharmacol Res. 2016 Jun;108:31-38. doi: 10.1016/j.phrs.2016.04.012. Epub 2016 Apr 20.
Several data gathered in the last decade indicate an increase of abuse of prescription opioid drugs oxycodone (OXY) and hydrocodone (HYDRO) in women. However, to date there are no conclusive evidences investigating the gender-dependent abuse liability of prescription opioids. This study aims to supply a specific focus on women's data through a selective summary of the literature analyzing gender differences in the pharmacokinetic and pharmacodynamic dimension of OXY and HYDRO. Findings from this study suggest that the majority of OXY and HYDRO pharmacokinetic and pharmacodynamic effects do not differ according to gender, though confirming a significant difference in the incidence of adverse effects as demonstrated by the increased gastrointestinal adverse reactions in female subjects. Although the majority of recent clinical studies include an equal number of female and male subjects, the main outcome parameters do not relate specifically to gender differences. Due to the gender influence in activity of CYP3A4 and its crucial role in metabolism of both OXY than HYDRO, we suggest that assessing pharmacokinetic and pharmacodynamic interactions in clinical studies may be useful to clarify the effect of the higher CYP3A4 activity in female in relation to CYP2D6 genotype. Overall, considering the paucity of data regarding gender differences in European Union, this work highlights that impact of new abuse deterrent formulations should be assessed with a special focus on data concerning female subjects.
过去十年中的多项数据表明,处方类阿片药物羟考酮(OXY)和氢可酮(HYDRO)在女性中的滥用情况有所增加。然而,迄今为止,还没有确凿的证据表明处方类阿片药物的滥用倾向存在性别差异。本研究旨在通过选择性综述文献,重点关注女性数据,分析 OXY 和 HYDRO 在药代动力学和药效学方面的性别差异。该研究结果表明,OXY 和 HYDRO 的大多数药代动力学和药效学效应并无明显性别差异,但女性受试者的胃肠道不良反应发生率较高,证实了性别差异确实存在。尽管大多数最近的临床研究都纳入了数量相等的女性和男性受试者,但主要的结果参数并未具体涉及性别差异。由于 CYP3A4 的活性在性别方面存在差异,并且其在 OXY 和 HYDRO 的代谢中起着至关重要的作用,我们建议在临床研究中评估药代动力学和药效学的相互作用可能有助于阐明女性 CYP3A4 活性较高与 CYP2D6 基因型之间的关系。总体而言,鉴于欧盟关于性别差异的数据相对较少,这项研究强调,应特别关注女性受试者的数据,评估新型防滥用配方的影响。
Pharmacol Res. 2016-4-20
J Clin Psychopharmacol. 2003-8
Psychopharmacology (Berl). 2010-7-28
J Clin Pharmacol. 2009-9-15
Eur J Clin Pharmacol. 2010-9-21
Brain Res. 2017-11-1
Clin Pharmacokinet. 2019-6
J Med Toxicol. 2012-12
Subst Abuse Rehabil. 2020-9-29
Front Pharmacol. 2018-10-1
Curr Opin Psychiatry. 2017-7