Katholieke Universiteit Leuven, Department of Occupational, Environmental and Insurance Medicine, B-3000 Leuven, Belgium.
J Clin Pharmacol. 2010 Jun;50(6):667-78. doi: 10.1177/0091270009347872. Epub 2010 Jan 23.
Delivery rates and plasma concentrations vary among patients treated with fentanyl patches. Absorption and urinary excretion characteristics of fentanyl were studied in patients undergoing palliative care. Almost 500 patches were analyzed for residual fentanyl content. Fentanyl and norfentanyl levels were determined in the urine of 50 patients. General and mixed effects linear regression models were established for the relationship between fentanyl dose rate and urinary excretion and to incorporate influencing factors. For different patch nominal dose strengths, wide but comparable variability in estimated dose rate and delivery efficiency was observed (coefficients of variation of 15% to 17%). Fentanyl delivery efficiency was 8.5% higher for patches of 25 microg/h as compared to 75 microg/h and, accordingly, 7.5% for patch application on the arm as compared to the leg. Urinary fentanyl and norfentanyl concentrations varied considerably. The general linear model revealed a positive effect of the calculated transdermal dose rate on urinary fentanyl levels, explaining 34% of the variability (P < .0001). In addition, gender (P = .04) and type of cancer pathology (P = .03) exerted significant effects on the linear model, explaining 40% and 64% of the variability, respectively. Delivery efficiency of fentanyl patches can vary substantially, possibly leading to either underdosing or overdosing.
接受芬太尼贴剂治疗的患者之间，其药物释放率和血药浓度存在差异。我们研究了接受姑息治疗的患者中芬太尼的吸收和尿排泄特征。对近 500 片芬太尼贴剂进行了残留芬太尼含量分析。对 50 名患者的尿液进行了芬太尼和去甲芬太尼水平检测。建立了芬太尼剂量率与尿排泄之间的关系以及纳入影响因素的通用和混合效应线性回归模型。对于不同的贴剂标称剂量强度，估计的剂量率和释放效率存在广泛但可比的变异性（变异系数为 15%至 17%）。与 75μg/h 的贴剂相比，25μg/h 的贴剂的释放效率高 8.5%，相应地，与腿部贴剂相比，手臂贴剂的释放效率高 7.5%。尿中芬太尼和去甲芬太尼浓度差异很大。一般线性模型显示，经皮剂量率的计算对尿中芬太尼水平有正效应，可解释 34%的变异性（P<0.0001）。此外，性别（P=0.04）和癌症病理类型（P=0.03）对线性模型有显著影响，分别解释了 40%和 64%的变异性。芬太尼贴剂的释放效率可能会有很大差异，这可能导致剂量不足或过量。
