Lovastatin therapy in receptor-negative homozygous familial hypercholesterolemia: lack of effect on low-density lipoprotein concentrations or turnover.
To determine whether at least part of the fall in low density lipoprotein (LDL) levels during lovastatin therapy might be the result of a reduced secretion of lipoproteins by the liver, three children 6 to 9 years of age with receptor-negative homozygous familial hypercholesterolemia underwent treatment with lovastatin. These patients have no capacity to synthesize LDL receptors. During lovastatin therapy, at a dose of 2 mg/kg/day, there was no decrease in LDL-cholesterol levels, nor was the turnover rate of LDL affected by the drug. The only significant change was a 74% drop in very low-density lipoprotein during treatment. We conclude that lovastatin is not effective in treatment of receptor-negative homozygous familial hypercholesterolemia. The most likely mechanism of action for this drug is to increase LDL receptor activity.
Uauy
R
R
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9052.
Vega
G L
GL
Grundy
S M
SM
Bilheimer
D M
DM
D001055:Apolipoproteins B / Q000097:blood; D002648:Child; D002784:Cholesterol / Q000097:blood; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008148:Lovastatin / Q000627:therapeutic use*; D008297:Male; D011973:Receptors, LDL / Q000378:metabolism
D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; D002784:Cholesterol; D008148:Lovastatin