Bláha M, Vlcková H, Nováková L, Solichová D, Solich P, Lánská M, Malý J, Bláha V
2nd Department of Internal Medicine, Hematology, Medical Faculty and Teaching Hospital, Charles University, Hradec Králové, Czech Republic.
J Biomed Biotechnol. 2011;2011:912472. doi: 10.1155/2011/912472. Epub 2010 Nov 7.
Using our statin analysis method, it was possible to uncover a significant drop in statin levels (atorvastatin, simvastatin, and metabolites) after extracorporeal LDL-cholesterol elimination (EE) in severe familial hypercholesterolemia (FH). The purpose of this work was to identify the mechanism underlying this drop and its clinical significance as well as to propose measures to optimize a pharmacotherapeutical regimen that can prevent the loss of statins.
Ultra High Performance Liquid Chromatography (UHPLC) connected to the triple quadrupole MS/MS system was used. Patients. A group of long-term treated patients (3-12 years of treatment) with severe FH (12 patients) and treated regularly by LDL-apheresis (immunoadsorption) or haemorheopheresis (cascade filtration) were included in this study.
After EE, the level of statins and their metabolites decreased (atorvastatin before/after LDL-apheresis: 8.83/3.46 nmol/l; before/after haemorheopheresis: 37.02/18.94 nmol/l). A specific loss was found (concentration of atorvastatin for LDL-apheresis/haemorheopheresis: 0.28/3.04 nmol/l in washing fluids; 11.07 nmol/l in filters). To prevent substantial loss of statin concentrations, a pharmacotherapeutic regimen with a longer time interval between the dose of statins and EE is recommended (15 hours).
A specific loss of statins was found in adsorbent columns and filters. The decrease can be prevented by the suggested dosage scheme.
运用我们的他汀类药物分析方法，发现在重度家族性高胆固醇血症（FH）患者进行体外低密度脂蛋白胆固醇清除（EE）后，他汀类药物（阿托伐他汀、辛伐他汀及其代谢产物）水平显著下降。本研究旨在确定这种下降的潜在机制及其临床意义，并提出优化药物治疗方案以防止他汀类药物流失的措施。
采用与三重四极杆串联质谱系统联用的超高效液相色谱（UHPLC）。患者。本研究纳入了一组长期接受治疗（治疗3 - 12年）的重度FH患者（12例），他们定期接受低密度脂蛋白吸附（免疫吸附）或血液滤过（级联过滤）治疗。
EE后，他汀类药物及其代谢产物水平下降（阿托伐他汀在低密度脂蛋白吸附前后：8.83/3.46 nmol/l；血液滤过前后：37.02/18.94 nmol/l）。发现了特定的损失（低密度脂蛋白吸附/血液滤过中阿托伐他汀在冲洗液中的浓度：0.28/3.04 nmol/l；在滤器中的浓度为11.07 nmol/l）。为防止他汀类药物浓度大幅下降，建议采用他汀类药物给药与EE之间时间间隔更长的药物治疗方案（15小时）。
在吸附柱和滤器中发现了他汀类药物的特定损失。通过建议的给药方案可防止这种下降。
