DETERMINATION OF CHANGES IN SERUM LATHOSTEROL DURING TREATMENT WITH SIMVASTATIN TO EVALUATE THE ROLE OF LATHOSTEROL AS A PARAMETER FOR WHOLE-BODY CHOLESTEROL-SYNTHESIS

Serum levels of cholesterol and the cholesterol precursor lathosterol were determined in five healthy volunteers who took 20 mg simvastatin daily during 1 week. During this period and for the following 5 days b lood samples were collected. Five days after ingestion of simvastatin, serum lathosterol had already reached a steady-state level and its co ncentration decreased by 55-73%. In contrast, the cholesterol concentr ation decreased only by 17-29% and did not reach a steady-state level even after 7 days of treatment. After withdrawal of simvastatin, serum lathosterol quickly rose to pretreatment values. From the data a mean half-life of lathosterol could be calculated of 23.5 +/- 6.6 h during treatment with simvastatin and of 28.7 +/- 15.1 h after its withdrawa l, taking, respectively, the decrease and increase of serum lathostero l into account. From these data it can be concluded that serum lathost erol is also a good parameter for determining whole body cholesterol s ynthesis during non-steady-state conditions, although plasma mevalonic acid, another (early) cholesterol precursor, is preferred owing to it s much shorter reported half-life.