Use of cholesterol precursors to assess changes in cholesterol synthesis under non-steady-state conditions.

摘要: Background Quantification of plasma levels an early and late intermediate on the cholesterol pathway, mevalonic acid (MVA) lathosterol respectively, provides a useful method estimating synthesis in humans. The aim this study was to assess further their roles as indices under non-steady-state conditions. Methods The short-term effects pharmacological inhibition 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase both variables were determined four normolipidaemic subjects during after treatment with simvastatin 20 mg daily. Plasma MVA measured using gas chromatography–mass spectrometry, chromatography. Results A single dose decreased 2 h lathosterol–cholesterol (L/C) ratio 4 h. Treatment daily for 9 days by approximately 50%, nadir occurring second day L/C fifth day, resulted 39% reduction low-density lipoprotein (LDL)-cholesterol. After discontinuing simvastatin, there rebounds above basal but not LDL or apolipoprotein B (apoB), latter continuing decrease 2 days. Conclusion These results suggest that rapidly down-regulates synthesis, which is then up-regulated when drug withdrawn.