Kharasch Evan D, Hoffer Christine, Whittington Dale
Department of Anesthesiology, University of Washington, Seattle, Washington 98195, USA.
Anesthesiology. 2004 Sep;101(3):738-43. doi: 10.1097/00000542-200409000-00023.
Cancer pain is primarily a problem of older persons. Oral transmucosal fentanyl citrate (OTF) was developed to provide rapid analgesia and is the first drug specifically approved for treating breakthrough cancer pain. Fentanyl in OTF is absorbed across the oral mucosa but a considerable portion is swallowed and absorbed enterally. The effects of age on OTF pharmacokinetics and pharmacodynamics are unknown. This investigation evaluated OTF disposition and clinical effects in older (60-75 yr) compared with younger (18-40 yr) volunteers.
Healthy young (26 +/- 6 yr) and older (67 +/- 6 yr) volunteers (n = 12 each) were studied in an Institutional Review Board approved protocol. They received OTF (10 microg/kg). Plasma fentanyl and norfentanyl concentrations were determined by mass spectrometry. Fentanyl effects were measured by dark-adapted pupil diameter and by subjective self-assessments using visual analog scales.
Plasma fentanyl and norfentanyl concentrations and pharmacokinetic parameters did not differ between younger and older subjects. Maximum pupil diameter change from baseline was significantly less in older (3.1 +/- 0.7 mm) compared with younger (4.5 +/- 1.1 mm) subjects (P < 0.05). OTF-dependent subjective assessments of alertness/sedation, energy level, confusion, clumsiness, anxiety, and nausea did not differ in the older subjects.
The pharmacokinetics of OTF were not altered in older volunteers. In contrast, there was a somewhat diminished response to the miotic effects of fentanyl in older subjects. No change in OTF dosing in the elderly would appear necessary because of altered pharmacokinetics. If the response to OTF in older patients is similar to that in older volunteers and miosis is representative of analgesia and respiratory depression, then changes in OTF dosing with age alone do not appear indicated.
癌痛主要是老年人面临的问题。口腔黏膜枸橼酸芬太尼（OTF）被研发用于提供快速镇痛，是首个专门获批用于治疗癌痛突发加剧的药物。OTF中的芬太尼可通过口腔黏膜吸收，但相当一部分会被吞咽并经肠道吸收。年龄对OTF药代动力学和药效动力学的影响尚不清楚。本研究评估了老年（60 - 75岁）与年轻（18 - 40岁）志愿者中OTF的处置情况及临床效果。
在机构审查委员会批准的方案中对健康年轻（26±6岁）和老年（67±6岁）志愿者（各12名）进行研究。他们接受OTF（10微克/千克）。通过质谱法测定血浆芬太尼和去甲芬太尼浓度。通过暗适应瞳孔直径以及使用视觉模拟量表进行主观自我评估来测量芬太尼的效果。
年轻和老年受试者的血浆芬太尼和去甲芬太尼浓度及药代动力学参数并无差异。与年轻（4.5±1.1毫米）受试者相比，老年（3.1±0.7毫米）受试者从基线开始的最大瞳孔直径变化显著更小（P<0.05）。老年受试者中OTF依赖的警觉/镇静、能量水平、困惑、笨拙、焦虑和恶心的主观评估并无差异。
老年志愿者中OTF的药代动力学未改变。相比之下，老年受试者对芬太尼缩瞳作用的反应有所减弱。由于药代动力学改变，老年患者的OTF剂量似乎无需调整。如果老年患者对OTF的反应与老年志愿者相似，且瞳孔缩小代表镇痛和呼吸抑制，那么仅因年龄改变OTF剂量似乎并无必要。
