Effects of pravastatin and cholestyramine on products of the mevalonate pathway in familial hypercholesterolemia.

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Elmberger PG, Kalen A, Lund E, Reihner E, Eriksson M, Berglund L, Angelin B, Dallner G

Effects of pravastatin and cholestyramine on products of the mevalonate pathway in familial hypercholesterolemia.

J Lipid Res. 1991 Jun;32(6):935-40.

PubMed ID

1940625 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Pharmaco-metabolomics

Drug	Drug Groups	Metabolite	Change	Description
Pravastatin	Approved	Ubiquinone	decreased	Pravastatin decreases the level of Ubiquinone in the blood
Pravastatin	Approved	Lathosterol	decreased	Pravastatin decreases the level of Lathosterol in the blood