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 blood samples were collected. Five days after ingestion of simvastatin, serum lathosterol had already reached a steady-state level and its concentration decreased by 55-73%. In contrast, the cholesterol concentration 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 withdrawal, taking, respectively, the decrease and increase of serum lathosterol into account. From these data it can be concluded that serum lathosterol is also a good parameter for determining whole body cholesterol synthesis during non-steady-state conditions, although plasma mevalonic acid, another (early) cholesterol precursor, is preferred owning to its much shorter reported half-life.