Effects of pravastatin and cholestyramine on products of the mevalonate pathway in familial hypercholesterolemia.
Patients with heterozygous familial hypercholesterolemia (n = 12) were treated either with pravastatin, a specific inhibitor of HMG-CoA reductase, or cholestyramine, followed by a period of combined treatment with both drugs. Initially, these patients had increased serum levels of low density lipoprotein (LDL) cholesterol (8.77 +/- 0.48 mmol/l; SEM), lathosterol (5.32 +/- 0.60 mg/l), and ubiquinone (0.76 +/- 0.09 mg/l), while the serum dolichol concentration was in the normal range. Cholestyramine treatment (n = 6) decreased the levels of LDL cholesterol (-32%) and increased lathosterol (+125%), but did not change dolichol or ubiquinone levels in a significant manner. Pravastatin treatment (n = 6) decreased LDL cholesterol (-27%), lathosterol (-46%), and ubiquinone (-29%). In this case, the amount of dolichol in serum also showed a small but statistically insignificant decrease (-16%) after 12 weeks of treatment. Combined treatment with cholestyramine and pravastatin (n = 6) resulted in changes that were similar to, but less pronounced than, those observed during pravastatin treatment alone. In no case was the ratio between ubiquinone and LDL cholesterol reduced. Possible effects on hepatic cholesterol, ubiquinone, and dolichol concentrations were studied in untreated (n = 2), cholestyramine-treated (n = 2), and pravastatin-treated (n = 4) gallstone patients and no consistent changes could be observed. The results indicate that treatment with pravastatin in familial hypercholesterolemia decreases serum ubiquinone levels in proportion to the reduction in LDL cholesterol.
Department of Clinical Pathology, Huddinge University Hospital, Karolinska Institutet, Sweden.
P G
PG
Elmberger
A
A
Kalén
E
E
Lund
E
E
Reihnér
M
M
Eriksson
L
L
Berglund
B
B
Angelin
G
G
Dallner
D000328:Adult; D000368:Aged; D002784:Cholesterol / Q000097:blood; D002792:Cholestyramine Resin / Q000494:pharmacology* / Q000627:therapeutic use; D004286:Dolichols / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000096:biosynthesis; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy / Q000201:enzymology*; D008297:Male; D008798:Mevalonic Acid / Q000378:metabolism*; D008875:Middle Aged; D017035:Pravastatin / Q000494:pharmacology* / Q000627:therapeutic use; D014451:Ubiquinone / Q000097:blood
D004286:Dolichols; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002792:Cholestyramine Resin; D014451:Ubiquinone; C001521:lathosterol; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D017035:Pravastatin; D008798:Mevalonic Acid