Contrasting effects of lovastatin and cholestyramine on low-density lipoprotein cholesterol and 24-hour urinary mevalonate excretion in patients with heterozygous familial hypercholesterolemia.
To further validate the usefulness of quantitative measurements of urinary mevalonic acid excretion as an indicator of rates of cholesterol biosynthesis, we have determined the 24-hour urinary excretion of mevalonic acid in patients with heterozygous familial hypercholesterolemia treated with drugs that have opposing effects on cholesterol biosynthesis. In patients with familial hypercholesterolemia treated with the bile acid sequestrant cholestyramine (16 gms/day), urinary mevalonate excretion increased by 28%, whereas low-density lipoprotein cholesterol concentrations decreased by 21%. In patients with familial hypercholesterolemia treated with the 3-hydroxy 3-methyl glutaryl coenzyme A reductase inhibitor lovastatin (80 mg/day), concentrations of low-density lipoprotein cholesterol and the urinary excretion of mevalonate both decreased (by 40% and 34%, respectively). When cholestyramine was used in combination with lovastatin, low-density lipoprotein cholesterol levels decreased by an additional 14% as compared to monotherapy with lovastatin; urinary mevalonate excretion rose by (25%), but the magnitude of this increase was not statistically significant. We conclude that rates of excretion of urinary mevalonic acid (which may reflect rates of whole body cholesterol biosynthesis) in patients with FH decrease on therapy with lovastatin and increase in response to cholestyramine treatment. When used in combination, these drugs counteract each other's effects on cholesterol synthesis, but low-density lipoprotein cholesterol concentrations decrease further. Measurement of urinary mevalonate excretion affords a practical means of assessing the comparable effects of different dietary or pharmaceutical manipulations on cholesterol biosynthesis in human beings.
Pappu
A S
AS
Department of Medicine, Oregon Health Sciences University, Portland 97201.
Illingworth
D R
DR
D000328:Adult; D008078:Cholesterol, LDL / Q000097:blood*; D002792:Cholestyramine Resin / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008148:Lovastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008798:Mevalonic Acid / Q000652:urine*
D008078:Cholesterol, LDL; D002792:Cholestyramine Resin; D008148:Lovastatin; D008798:Mevalonic Acid