Protein binding of fentanyl and its metabolite nor-fentanyl in human plasma, albumin and α-1 acid glycoprotein
Protein binding of fentanyl and its metabolite nor-fentanyl in human plasma, albumin and α-1 acid glycoprotein
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DOI：
10.3109/00498254.2014.971093
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发表时间：
2015-03-01
期刊：
影响因子：
1.8
通讯作者：
Norris, Ross
中科院分区：
文献类型：
--
作者：
Bista, Sudeep Raj;Haywood, Alison;Norris, Ross
1.芬太尼是一种高度亲脂性的阿片类药物，常用于治疗癌症疼痛。芬太尼在人血浆中的血浆蛋白结合率（PPB）据报道为80- 85%，但目前尚不清楚芬太尼是否主要与白蛋白（ALB）或α-1酸性糖蛋白（AAG）结合，也没有对代谢产物去甲芬太尼进行研究。芬太尼还已知会与塑料器皿和超滤（UF）装置结合，对结合实验产生不利影响。定量芬太尼和去甲芬太尼对等渗磷酸盐缓冲液和接种人血浆中ALB和AAG的PPB。PPB也在从接受透皮芬太尼的癌症患者获得的血浆样品中进行。还评估了芬太尼和去甲芬太尼在PPB研究中常用的UF装置和塑料器皿上的吸附。芬太尼主要与ALB结合，而不是AAG，去甲芬太尼与血浆蛋白的结合可忽略不计。芬太尼的总PPB在接种人血浆中为86-89%。56例癌症患者样本中芬太尼的PPB为95.1 ± 3.52%，去甲芬太尼为32.4 ± 21.9%。UF被证明是PPB研究的可靠和方便的方法，从而消除了在UF过程中对药物吸附到塑料器皿的复杂测试的需要。
1. Fentanyl is a highly lipophilic opioid commonly used to treat cancer pain. Plasma protein binding (PPB) of fentanyl in human plasma is reported as 80-85%, however it is unclear whether fentanyl binds primarily to albumin (ALB) or alpha-1 acid glycoprotein (AAG) and no studies have been conducted on the metabolite, nor-fentanyl. Fentanyl is also known to bind to plasticware and ultrafiltration (UF) devices which impacts adversely on binding experiments.2. PPB of fentanyl and nor-fentanyl to ALB and AAG in isotonic phosphate buffer solution and seeded human plasma was quantified. PPB was also performed in plasma samples obtained from cancer patients receiving transdermal fentanyl. The adsorption of fentanyl and norfentanyl to UF devices and plasticware commonly used in PPB studies was also assessed.3. Fentanyl was shown to bind primarily to ALB as opposed to AAG, with nor-fentanyl exhibiting negligible binding to plasma proteins. Total PPB of fentanyl was 86-89% in seeded human plasma. PPB in 56 cancer patient samples was 95.1 +/- 3.52% for fentanyl and 32.4 +/- 21.9% for nor-fentanyl.4. UF was shown to be a reliable and convenient method for PPB studies, thereby removing the need for complex testing for adsorption of the drug to plasticware during UF.