BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: A specific loss of statins was found in adsorbent columns and filters. The decrease can be prevented by the suggested dosage scheme.
- MeSH
- anticholesteremika krev metabolismus MeSH
- dospělí MeSH
- hemofiltrace metody MeSH
- hyperlipoproteinemie typ II krev farmakoterapie terapie MeSH
- kyseliny heptylové krev metabolismus MeSH
- LDL-cholesterol izolace a purifikace MeSH
- lidé středního věku MeSH
- lidé MeSH
- neparametrická statistika MeSH
- pyrroly krev metabolismus MeSH
- separace krevních složek metody MeSH
- simvastatin krev metabolismus MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Acetylcholinesterase (AChE) inhibitors represent standard treatment of Alzheimer´s disease. Cholesterol plays an important role in Alzheimer´s disease development. Because cholesterol synthesis may be inhibited by statins or bisphosphonates, we hypothesized that these drugs might possibly have an influence on cholinesterases. Moreover, we also evaluated if the cholesterol-lowering agents that cross the blood-brain barrier (e.g. simvastatin) should be more effective than those which do not (e.g. atorvastatin). Four groups of rats were orally administered simvastatin, atorvastatin, alendronate or vehicle for seven days. Thereafter, blood samples were taken and the basal ganglia, septum, frontal cortex, and hippocampus were isolated from brains for measurement of acetylcholinesterase activity. In the blood, activities of neither acetyl- nor butyrylcholinesterase were influenced by any of the applied drugs. In the brain, no significant changes in AChE activity were observed after administration of atorvastatin. Both simvastatin and alendronate significantly suppressed the activity of AChE in the frontal cortex. In conclusion, our results confirmed the hypothesis that cholesterol-modifying drugs modulate AChE activity and it is more reasonable to use a blood-brain barrier penetrating drug.
- MeSH
- acetylcholinesterasa krev účinky léků MeSH
- alendronát krev metabolismus terapeutické užití MeSH
- Alzheimerova nemoc farmakoterapie krev MeSH
- cholesterol krev metabolismus MeSH
- financování organizované využití MeSH
- potkani Wistar MeSH
- simvastatin krev metabolismus terapeutické užití MeSH
- statiny terapeutické užití MeSH
- MeSH
- arterioskleróza farmakoterapie metabolismus MeSH
- hypolipidemika farmakologie klasifikace terapeutické užití MeSH
- lidé MeSH
- lovastatin metabolismus škodlivé účinky terapeutické užití MeSH
- pravastatin metabolismus škodlivé účinky terapeutické užití MeSH
- simvastatin metabolismus škodlivé účinky terapeutické užití MeSH
- statiny klasifikace metabolismus terapeutické užití MeSH
- Check Tag
- lidé MeSH
- MeSH
- finanční podpora výzkumu jako téma MeSH
- gemfibrozil farmakologie chemie klasifikace MeSH
- hypercholesterolemie metabolismus terapie MeSH
- hyperlipidemie metabolismus terapie MeSH
- hypolipidemika farmakologie chemie normy MeSH
- lidé MeSH
- metabolický syndrom farmakoterapie terapie MeSH
- simvastatin farmakokinetika klasifikace metabolismus MeSH
- Check Tag
- lidé MeSH
- MeSH
- finanční podpora výzkumu jako téma MeSH
- krysa rodu rattus MeSH
- kyselina kainová metabolismus toxicita MeSH
- limbický systém patologie účinky léků MeSH
- neuroprotektivní látky farmakologie metabolismus terapeutické užití MeSH
- simvastatin farmakologie metabolismus terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
