Kalitynski Rafal, Dawidowicz Andrzej L, Poszytek Jacek
Department of Chromatographic Methods, Maria Curie-Sklodowska University, Lublin PL 20 031, Poland.
Acta Pharmacol Sin. 2006 Dec;27(12):1637-41. doi: 10.1111/j.1745-7254.2006.00454.x.
It is generally assumed that only unbound drugs can reach the site of action by diffusing across the membranes and exerting pharmacological effects by interacting with receptors. Recent research has shown that the percentage of free drugs may depend on the total drug concentration. The aim of the paper is to verify whether the mentioned dependence reported for propofol also takes place in plasma and human serum albumin samples in the presence of intralipid-the medium used as a vehicle for propofol infusions and a parenteral nutrition agent.
Artificial plasma samples and human plasma were spiked with intralipid or ethanolic solutions of propofol. The samples were then assayed for free propofol concentration using ultrafiltration and high performance liquid chromatography with fluorimetric detection.
The decrease of the total drug concentration results in free propofol fraction increase, irrespectively of the used type of propofol solvent and sample type. The addition of intralipid causes the lowering of the overall free drug fraction with respect to the samples spiked with ethanolic solutions of the drug.
The presence of intralipid does not influence the phenomenon of free propofol fraction rise at low total drug concentration. Such a rise cannot be ignored in clinical conditions when the drug is applied for sedative, antiemetic or other low-dosage purposes.
一般认为只有游离药物能够通过跨膜扩散到达作用部位,并通过与受体相互作用发挥药理作用。最近的研究表明,游离药物的百分比可能取决于总药物浓度。本文的目的是验证在丙泊酚输注和肠外营养制剂中使用的介质——脂肪乳剂存在的情况下,丙泊酚所报道的上述依赖性在血浆和人血清白蛋白样本中是否也会发生。
用脂肪乳剂或丙泊酚乙醇溶液对人工血浆样本和人血浆进行加样。然后使用超滤和带荧光检测的高效液相色谱法测定样本中游离丙泊酚的浓度。
无论使用何种类型的丙泊酚溶剂和样本类型,总药物浓度的降低都会导致游离丙泊酚分数增加。相对于用药物乙醇溶液加样的样本,脂肪乳剂的添加会导致总体游离药物分数降低。
脂肪乳剂的存在不影响总药物浓度较低时游离丙泊酚分数升高的现象。当药物用于镇静、止吐或其他低剂量用途时,在临床情况下这种升高不能被忽视。