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.
De Cuyper
I
I
Central Laboratory for Clinical Chemistry, University Hospital, Groningen, Netherlands.
Wolthers
B G
BG
van Doormaal
J J
JJ
Wijnandts
P N
PN
D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002784:Cholesterol / Q000096:biosynthesis* / Q000097:blood* / Q000502:physiology; D002849:Chromatography, Gas; D005260:Female; D006207:Half-Life; D006801:Humans; D007536:Isomerism; D007700:Kinetics; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008798:Mevalonic Acid / Q000097:blood; D019821:Simvastatin
D000924:Anticholesteremic Agents; C001521:lathosterol; D002784:Cholesterol; D008148:Lovastatin; D019821:Simvastatin; D008798:Mevalonic Acid