Skip to main content
PMC home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1995 Feb;39(2):135–141. doi: 10.1111/j.1365-2125.1995.tb04420.x

A comparison of the effects of simvastatin and pravastatin monotherapy on muscle histology and permeability in hypercholesterolaemic patients.

J Contermans 1, J W Smit 1, P R Bär 1, D W Erkelens 1
PMCID: PMC1364950  PMID: 7742151

Abstract

1. In this double-blind, placebo controlled, prospective study, it was assessed whether simvastatin or pravastatin monotherapy have adverse effects on muscle histology and muscle membrane permeability in hypercholesterolaemic patients. 2. Twenty-four patients, seven females and 17 males, with primary hypercholesterolaemia (LDL cholesterol levels > or = 4.14 mmol l-1) were selected from the outpatient lipid clinic of a 650 bed academic medical centre. 3. After a 6-week lipid lowering diet and placebo period, patients were randomized into two groups of 12 subjects with similar characteristics, to receive either simvastatin or pravastatin in dosages of 10-40 mg day-1 for three periods of 6 weeks. After each 3-week period the dose was adjusted to LDL cholesterol to aim for equipotent dosage. 4. All subjects performed a 45 min, lean body mass standardized bicycle ergometer test, before and after 18 weeks of treatment. As parameter for muscle damage, the exercise-induced rise of the muscle proteins, creatine kinase (CK) and myoglobin (Mb), relative to pre-exercise levels, were determined 1 and 8 h after the test. Forty-eight hours after each test a biopsy was taken from the quadriceps muscle and histology was judged by three independent observers. 5. Eighteen weeks of monotherapy with simvastatin and pravastatin did not affect the exercise induced release of CK and Mb, neither were any differences observed in muscle histology before and after treatment with either of the drugs. 6. Although simvastatin doses were lower than pravastatin, reductions in total- and LDL-cholesterol were greater in the simvastatin treated patients than in the pravastatin treated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
138

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ayanian J. Z., Fuchs C. S., Stone R. M. Lovastatin and rhabdomyolysis. Ann Intern Med. 1988 Oct 15;109(8):682–683. doi: 10.7326/0003-4819-109-8-682. [DOI] [PubMed] [Google Scholar]
  2. Bhatnagar D., Durrington P. N., Neary R., Miller J. P. Elevation of skeletal muscle isoform of serum creatine kinase in heterozygous familial hypercholesterolaemia. J Intern Med. 1990 Nov;228(5):493–495. doi: 10.1111/j.1365-2796.1990.tb00268.x. [DOI] [PubMed] [Google Scholar]
  3. Borleffs J. C., Derksen R. H., Bär D. P. Serum myoglobin and creatine kinase concentrations in patients with polymyositis or dermatomyositis. Ann Rheum Dis. 1987 Feb;46(2):173–174. doi: 10.1136/ard.46.2.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bradford R. H., Shear C. L., Chremos A. N., Dujovne C., Downton M., Franklin F. A., Gould A. L., Hesney M., Higgins J., Hurley D. P. Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. I. Efficacy in modifying plasma lipoproteins and adverse event profile in 8245 patients with moderate hypercholesterolemia. Arch Intern Med. 1991 Jan;151(1):43–49. doi: 10.1001/archinte.151.1.43. [DOI] [PubMed] [Google Scholar]
  5. Corpier C. L., Jones P. H., Suki W. N., Lederer E. D., Quinones M. A., Schmidt S. W., Young J. B. Rhabdomyolysis and renal injury with lovastatin use. Report of two cases in cardiac transplant recipients. JAMA. 1988 Jul 8;260(2):239–241. [PubMed] [Google Scholar]
  6. Deslypere J. P., Vermeulen A. Rhabdomyolysis and simvastatin. Ann Intern Med. 1991 Feb 15;114(4):342–342. doi: 10.7326/0003-4819-114-4-342_1. [DOI] [PubMed] [Google Scholar]
  7. Diepersloot R. J., Bouter K. P., Bruining G. J., Molenaar J. L., Hoekstra J. B., Masurel N., Erkelens D. W. No evidence for the enhanced production of insulin autoantibodies after confrontation with common viral antigens in insulin dependent diabetes mellitus. Neth J Med. 1990 Dec;37(5-6):225–230. [PubMed] [Google Scholar]
  8. Driessen-Kletter M. F., Amelink G. J., Bär P. R., van Gijn J. Myoglobin is a sensitive marker of increased muscle membrane vulnerability. J Neurol. 1990 Jul;237(4):234–238. doi: 10.1007/BF00314625. [DOI] [PubMed] [Google Scholar]
  9. East C., Alivizatos P. A., Grundy S. M., Jones P. H., Farmer J. A. Rhabdomyolysis in patients receiving lovastatin after cardiac transplantation. N Engl J Med. 1988 Jan 7;318(1):47–48. doi: 10.1056/NEJM198801073180111. [DOI] [PubMed] [Google Scholar]
  10. England J. D., Viles A., Walsh J. C., Stewart P. M. Muscle side effects associated with simvastatin therapy. Med J Aust. 1990 Nov 5;153(9):562–563. doi: 10.5694/j.1326-5377.1990.tb126217.x. [DOI] [PubMed] [Google Scholar]
  11. Friedewald W. T., Levy R. I., Fredrickson D. S. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972 Jun;18(6):499–502. [PubMed] [Google Scholar]
  12. Fukuyama Y., Suzuki Y., Hirayama Y., Harada J., Ohsawa M., Saito K., Ochiai E., Nakane A. Percutaneous needle muscle biopsy in the diagnosis of neuromuscular disorders in children. Histological, histochemical and electron microscopic studies. Brain Dev. 1981;3(3):277–287. doi: 10.1016/s0387-7604(81)80050-2. [DOI] [PubMed] [Google Scholar]
  13. Germershausen J. I., Hunt V. M., Bostedor R. G., Bailey P. J., Karkas J. D., Alberts A. W. Tissue selectivity of the cholesterol-lowering agents lovastatin, simvastatin and pravastatin in rats in vivo. Biochem Biophys Res Commun. 1989 Feb 15;158(3):667–675. doi: 10.1016/0006-291x(89)92773-3. [DOI] [PubMed] [Google Scholar]
  14. Grundy S. M. HMG-CoA reductase inhibitors for treatment of hypercholesterolemia. N Engl J Med. 1988 Jul 7;319(1):24–33. doi: 10.1056/NEJM198807073190105. [DOI] [PubMed] [Google Scholar]
  15. Herrmann F. H., Spiegler A., Wiedemann G. Muscle provocation test. A sensitive method for discrimination between carriers and noncarriers of Duchenne muscular dystrophy. Hum Genet. 1982;61(2):102–104. doi: 10.1007/BF00274196. [DOI] [PubMed] [Google Scholar]
  16. Illingworth D. R., Bacon S. Influence of lovastatin plus gemfibrozil on plasma lipids and lipoproteins in patients with heterozygous familial hypercholesterolemia. Circulation. 1989 Mar;79(3):590–596. doi: 10.1161/01.cir.79.3.590. [DOI] [PubMed] [Google Scholar]
  17. Israeli A., Raveh D., Arnon R., Eisenberg S., Stein Y. Lovastatin and elevated creatine kinase: results of rechallenge. Lancet. 1989 Apr 1;1(8640):725–725. doi: 10.1016/s0140-6736(89)92237-x. [DOI] [PubMed] [Google Scholar]
  18. Landis J. R., Koch G. G. The measurement of observer agreement for categorical data. Biometrics. 1977 Mar;33(1):159–174. [PubMed] [Google Scholar]
  19. Malini P. L., Ambrosioni E., De Divitiis O., Di Somma S., Rosiello G., Trimarco B. Simvastatin versus pravastatin: efficacy and tolerability in patients with primary hypercholesterolemia. Clin Ther. 1991 Jul-Aug;13(4):500–510. [PubMed] [Google Scholar]
  20. Meese R. B., Spritzer C. E., Negro-Vilar R., Bashore T., Herfkens R. J. Detection, characterization and functional assessment of reperfused Q-wave acute myocardial infarction by cine magnetic resonance imaging. Am J Cardiol. 1990 Jul 1;66(1):1–9. doi: 10.1016/0002-9149(90)90726-h. [DOI] [PubMed] [Google Scholar]
  21. Mol M. J., Erkelens D. W., Gevers Leuven J. A., Schouten J. A., Stalenhoef A. F. Simvastatin (MK-733): a potent cholesterol synthesis inhibitor in heterozygous familial hypercholesterolaemia. Atherosclerosis. 1988 Feb;69(2-3):131–137. doi: 10.1016/0021-9150(88)90006-8. [DOI] [PubMed] [Google Scholar]
  22. Norman D. J., Illingworth D. R., Munson J., Hosenpud J. Myolysis and acute renal failure in a heart-transplant recipient receiving lovastatin. N Engl J Med. 1988 Jan 7;318(1):46–47. doi: 10.1056/NEJM198801073180110. [DOI] [PubMed] [Google Scholar]
  23. Pan H. Y., DeVault A. R., Wang-Iverson D., Ivashkiv E., Swanson B. N., Sugerman A. A. Comparative pharmacokinetics and pharmacodynamics of pravastatin and lovastatin. J Clin Pharmacol. 1990 Dec;30(12):1128–1135. doi: 10.1002/j.1552-4604.1990.tb01856.x. [DOI] [PubMed] [Google Scholar]
  24. Pierce L. R., Wysowski D. K., Gross T. P. Myopathy and rhabdomyolysis associated with lovastatin-gemfibrozil combination therapy. JAMA. 1990 Jul 4;264(1):71–75. [PubMed] [Google Scholar]
  25. Reaven P., Witztum J. L. Lovastatin, nicotinic acid, and rhabdomyolysis. Ann Intern Med. 1988 Oct 1;109(7):597–598. doi: 10.7326/0003-4819-109-7-597_2. [DOI] [PubMed] [Google Scholar]
  26. Reust C. S., Curry S. C., Guidry J. R. Lovastatin use and muscle damage in healthy volunteers undergoing eccentric muscle exercise. West J Med. 1991 Feb;154(2):198–200. [PMC free article] [PubMed] [Google Scholar]
  27. Singhvi S. M., Pan H. Y., Morrison R. A., Willard D. A. Disposition of pravastatin sodium, a tissue-selective HMG-CoA reductase inhibitor, in healthy subjects. Br J Clin Pharmacol. 1990 Feb;29(2):239–243. doi: 10.1111/j.1365-2125.1990.tb03626.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Smith P. F., Eydelloth R. S., Grossman S. J., Stubbs R. J., Schwartz M. S., Germershausen J. I., Vyas K. P., Kari P. H., MacDonald J. S. HMG-CoA reductase inhibitor-induced myopathy in the rat: cyclosporine A interaction and mechanism studies. J Pharmacol Exp Ther. 1991 Jun;257(3):1225–1235. [PubMed] [Google Scholar]
  29. Vickers S., Duncan C. A., Vyas K. P., Kari P. H., Arison B., Prakash S. R., Ramjit H. G., Pitzenberger S. M., Stokker G., Duggan D. E. In vitro and in vivo biotransformation of simvastatin, an inhibitor of HMG CoA reductase. Drug Metab Dispos. 1990 Jul-Aug;18(4):476–483. [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES