Bahrami Flora, Rossi René Michel, De Nys Katelijne, Joerger Markus, Radenkovic Milena Cukic, Defraeye Thijs
Laboratory for Biomimetic Membranes and Textiles, Empa, Swiss Federal Laboratories for Materials Science and Technology, Lerchenfeldstrasse 5, St. Gallen CH-9014, Switzerland; ARTORG Center for Biomedical Engineering Research, University of Bern, Mittelstrasse 43, Bern CH-3012, Switzerland.
Laboratory for Biomimetic Membranes and Textiles, Empa, Swiss Federal Laboratories for Materials Science and Technology, Lerchenfeldstrasse 5, St. Gallen CH-9014, Switzerland.
Eur J Pharm Sci. 2024 Apr 1;195:106727. doi: 10.1016/j.ejps.2024.106727. Epub 2024 Feb 13.
Fentanyl transdermal patches are widely implemented for cancer-induced pain treatment due to the high potency of fentanyl and gradual drug release. However, transdermal fentanyl up-titration for opioid-naïve patients is difficult, which is why opioid treatment is often started with oral/iv morphine. Based on the daily dose of morphine, the initial dose of the fentanyl patch is decided upon. After reaching a stable level of pain, the switch is made from oral/iv morphine to transdermal fentanyl. There are standard calculation tools for transferring from oral/iv morphine to transdermal fentanyl, which is the same for all patients. By considering the variations in the physiology of the patients, a unique switching strategy cannot meet the needs of different patients. This study explores the outcome in terms of pain relief and minute ventilation during opioid therapy. For this, we used physics-based simulations on a virtually-generated population of patients, and we applied the same therapy to all patients. We could show that patients' physiology, such as gender, age, and weight, greatly impact the outcome of the therapy; as such, the correlation coefficient between pain intensity and age is 0.89, and the correlation coefficient between patient's weight and maximum plasma concentration of morphine and fentanyl is -0.98 and -0.97. Additionally, a different combination of the duration of overlap between morphine and fentanyl therapy with different doses of fentanyl was considered for the virtual patients to find the best opioid-switching strategy for each patient. We explored the impact of combining physiological features to determine the best-suited strategy for virtual patients. Our findings suggest that tailoring morphine and fentanyl therapy only based on a limited number of features is insufficient, and increasing the number of impactful physiological features positively influences the outcome of the therapy.
由于芬太尼效力高且药物缓释，芬太尼透皮贴剂被广泛用于癌症引起的疼痛治疗。然而，对于未使用过阿片类药物的患者，增加透皮芬太尼剂量很困难，这就是阿片类药物治疗通常从口服/静脉注射吗啡开始的原因。根据吗啡的每日剂量确定芬太尼贴剂的初始剂量。在疼痛达到稳定水平后，从口服/静脉注射吗啡转换为透皮芬太尼。有从口服/静脉注射吗啡转换为透皮芬太尼的标准计算工具，对所有患者都是相同的。考虑到患者生理机能的差异，单一的转换策略无法满足不同患者的需求。本研究探讨了阿片类药物治疗期间疼痛缓解和分钟通气方面的结果。为此，我们对虚拟生成的患者群体进行了基于物理的模拟，并对所有患者应用相同的治疗方法。我们可以证明，患者的生理机能，如性别、年龄和体重，对治疗结果有很大影响；例如，疼痛强度与年龄之间的相关系数为0.89，患者体重与吗啡和芬太尼的最大血浆浓度之间的相关系数分别为-0.98和-0.97。此外，对于虚拟患者，考虑了吗啡和芬太尼治疗重叠持续时间与不同剂量芬太尼的不同组合，以找到适合每个患者的最佳阿片类药物转换策略。我们探讨了结合生理特征以确定适合虚拟患者的最佳策略的影响。我们的研究结果表明，仅基于有限数量的特征来调整吗啡和芬太尼治疗是不够的，增加有影响的生理特征数量会对治疗结果产生积极影响。
