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Residual effects of lovastatin and simvastatin on urinary mevalonate excretions in patients with familial hypercholesterolemia.
J Lab Clin Med. 2003 Apr; 141(4):250-6.JL

Abstract

3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase inhibitors are widely used to decrease plasma cholesterol levels in patients with heterozygous familial hypercholesterolemia (FH) who are at increased risk of premature coronary artery disease. Tissue-culture and animal studies have indicated that administration of HMG CoA reductase inhibitors (eg, lovastatin, simvastatin, etc) induces a compensatory increase in the activity of HMG CoA reductase, both by increasing its synthesis and decreasing catabolism. To determine in human subjects whether cessation of therapy with this class of drugs leads to induction of HMG CoA reductase activity and above-normal rates of cholesterol biosynthesis, we measured urinary concentrations of mevalonic acid (an indicator of cholesterol biosynthesis) after the cessation of therapy with lovastatin and simvastatin (80 mg/day) in patients with heterozygous FH. Plasma concentrations of LDL increased promptly on discontinuation of reductase inhibitor therapy but did not increase above pretreatment levels at any point after drug discontinuation. Similarly, the 24-hour urinary excretion of mevalonic acid was reduced during treatment with lovastatin or simvastatin and increased promptly on discontinuation of drug but did not increase to levels exceeding those found at baseline when the patients were receiving dietary therapy only. We conclude that cessation of treatment with HMG CoA reductase inhibitors in patients with FH does not result in a rebound increase in cholesterol biosynthesis and that no rebound overshoot occurs in plasma concentrations of low-density-lipoprotein cholesterol.

Authors+Show Affiliations

Division of Endocrinology, Diabetes, and Clinical Nutrition, Department of Medicine, L-465, Oregon Health and Science University, Portland, OR 97201, USA. pappua@ohsu.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12677170

Citation

Pappu, Anuradha S., et al. "Residual Effects of Lovastatin and Simvastatin On Urinary Mevalonate Excretions in Patients With Familial Hypercholesterolemia." The Journal of Laboratory and Clinical Medicine, vol. 141, no. 4, 2003, pp. 250-6.
Pappu AS, Bacon SP, Illingworth DR. Residual effects of lovastatin and simvastatin on urinary mevalonate excretions in patients with familial hypercholesterolemia. J Lab Clin Med. 2003;141(4):250-6.
Pappu, A. S., Bacon, S. P., & Illingworth, D. R. (2003). Residual effects of lovastatin and simvastatin on urinary mevalonate excretions in patients with familial hypercholesterolemia. The Journal of Laboratory and Clinical Medicine, 141(4), 250-6.
Pappu AS, Bacon SP, Illingworth DR. Residual Effects of Lovastatin and Simvastatin On Urinary Mevalonate Excretions in Patients With Familial Hypercholesterolemia. J Lab Clin Med. 2003;141(4):250-6. PubMed PMID: 12677170.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Residual effects of lovastatin and simvastatin on urinary mevalonate excretions in patients with familial hypercholesterolemia. AU - Pappu,Anuradha S, AU - Bacon,Sandra P, AU - Illingworth,D Roger, PY - 2003/4/5/pubmed PY - 2003/4/30/medline PY - 2003/4/5/entrez SP - 250 EP - 6 JF - The Journal of laboratory and clinical medicine JO - J. Lab. Clin. Med. VL - 141 IS - 4 N2 - 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase inhibitors are widely used to decrease plasma cholesterol levels in patients with heterozygous familial hypercholesterolemia (FH) who are at increased risk of premature coronary artery disease. Tissue-culture and animal studies have indicated that administration of HMG CoA reductase inhibitors (eg, lovastatin, simvastatin, etc) induces a compensatory increase in the activity of HMG CoA reductase, both by increasing its synthesis and decreasing catabolism. To determine in human subjects whether cessation of therapy with this class of drugs leads to induction of HMG CoA reductase activity and above-normal rates of cholesterol biosynthesis, we measured urinary concentrations of mevalonic acid (an indicator of cholesterol biosynthesis) after the cessation of therapy with lovastatin and simvastatin (80 mg/day) in patients with heterozygous FH. Plasma concentrations of LDL increased promptly on discontinuation of reductase inhibitor therapy but did not increase above pretreatment levels at any point after drug discontinuation. Similarly, the 24-hour urinary excretion of mevalonic acid was reduced during treatment with lovastatin or simvastatin and increased promptly on discontinuation of drug but did not increase to levels exceeding those found at baseline when the patients were receiving dietary therapy only. We conclude that cessation of treatment with HMG CoA reductase inhibitors in patients with FH does not result in a rebound increase in cholesterol biosynthesis and that no rebound overshoot occurs in plasma concentrations of low-density-lipoprotein cholesterol. SN - 0022-2143 UR - https://www.unboundmedicine.com/medline/citation/12677170/Residual_effects_of_lovastatin_and_simvastatin_on_urinary_mevalonate_excretions_in_patients_with_familial_hypercholesterolemia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022214302930386 DB - PRIME DP - Unbound Medicine ER -