Skip to main content
SpringerLink
Log in

Effects of long-term ketoconazole therapy on serum lipid levels

  • Originals
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Summary

Serum cholesterol and triglycerides were determined in 36 patients receiving an 8-month course of oral ketoconazole 200 mg/day in order to study its effect on lipid metabolism. The mean serum cholesterol concentration had decreased by 15% (p<0.001) after 1 month, but on continued medication it returned to the pretreatment state; after discontinuation of therapy it increased transiently by 13% (p<0.001). Triglycerides increased during ketoconazole administration and at the end of the trial the mean triglyceride concentration was 48% higher than the baseline value (p<0.02). Although most lipid values during therapy lay within the normal ranges, 6 patients developed transient hypertriglyceridaemia. There was no correlation between the changes in lipids and peak serum ketoconazole levels. In one subject studied in more detail the concentration of very low density lipoprotein triglycerides rose during therapy, whereas high density lipoprotein cholesterol decreased slightly. The lipoprotein lipase activity in muscle and, in particular, in adipose tissue was significantly suppressed during ketoconazole treatment. Serum lipids and, if possible, serum lipoproteins should be carefully monitored in patients receiving long-term oral ketoconazole therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Symoens J, Moens M, Dom J, Scheijgrond H, Dony J, Schuermans V, Legendre R, Finestine N (1980) An evaluation of two years of clinical experience with ketoconazole. Rev Infect Dis 2: 674–687

    Google Scholar 

  2. Jones HE, Simpson MD, Artis M (1981) Oral ketoconazole. An effective and safe treatment for dermatophytosis. Arch Dermatol 117: 129–134

    Google Scholar 

  3. Pont A, Williams PL, Azhar S, Reitz RE, Bochra C, Smith ER, Stevens DA (1982) Ketoconazole blocks testosterone synthesis. Arch Int Med 142: 2137–2140

    Google Scholar 

  4. Pont A, Williams PL, Loose DS, Feldman D, Azhar S, Reitz RE, Bochra C, Stevens DA (1982) Ketoconazole blocks adrenal steroid synthesis. Ann Int Med 97: 370–372

    Google Scholar 

  5. Grosso DS, Boyden TW, Pamenter RW, Johnson DG, Stevens DA, Galgiani JN (1983) Ketoconazole inhibition of testicular secretion of testosterone and displacement of steroid hormones from serum transport proteins. Antimicrob Agents Chemother 23: 207–212

    Google Scholar 

  6. Engelhardt D, Mann K, Hörmann R, Braun S, Karl HJ (1983) Ketoconazole inhibits cortisol secretion of an adrenal adenoma in vivo and in vitro. Klin Wochenschr 61: 373–375

    Google Scholar 

  7. Rollman O, Lööf L (1983) Hepatic toxicity of ketoconazole. Br J Dermatol 108: 376–378

    Google Scholar 

  8. Lithell H, Boberg J (1977) A method of determining lipoprotein lipase activity in human adipose tissue. Scand J Clin Lab Invest 37: 551–561

    Google Scholar 

  9. Lithell H, Boberg J (1978) Determinations of lipoprotein lipase activity in human skeletal muscle tissue. Biochim Biophys Acta 528: 58–68

    Google Scholar 

  10. Arner P, Engfeldt P, Lithell H (1981) Site differences in the basal metabolism of subcutaneous fat in obese women. J Clin Endocrinol Metab 53: 948–952

    Google Scholar 

  11. Nilsson-Ehle P, Schotz MJ (1976) A stable radioactive substrate emulsion for assay of lipoprotein lipase. J Lipid Res 17: 536–541

    Google Scholar 

  12. Carlsson LA, Rössner SA (1972) A methodological study of an intravenous fat tolerance test with intralipid emulsion. Scand J Clin Lab Invest 29: 271–280

    Google Scholar 

  13. Hjelm M, deVerdier CH (1963) A methodological study of the enzymatic determination of glucose in blood. Scand J Clin Lab Invest 15: 415–428

    Google Scholar 

  14. Wide L, Olsson E (1974) Impaired early insulin response to glucose in non-diabetic patients with necrosis lipoidica. Horm Metab Res [Suppl ser] 5: 130–133

    Google Scholar 

  15. Rush RL, Leon L, Turrell J (1971) Automated simultaneous cholesterol and triglyceride determination on the Auto-Analyzer II Instrument. Adv Automat Anal 1: 503–507

    Google Scholar 

  16. Havel RJ, Eder HA, Bragdon JH (1955) The determination and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest 34: 1345–1353

    Google Scholar 

  17. Burstein M, Samaille J (1960) Sur un dosage rapide du cholésterol lié aux alfa et aux béta lipoprotéins du sérum. Clin Chim Acta 5: 609

    Google Scholar 

  18. Vessby B, Lithell H, Hellsing K, Östlund-Lindqvist A-M, Gustafsson I-B, Boberg J, Ledermann H (1980) Effects of bezafibrate on the serum lipoprotein lipid and apolipoprotein composition, lipoprotein triglyceride removal capacity and the fatty acid composition of the plasma lipid esters. Atherosclerosis 37: 257–269

    Google Scholar 

  19. Borgers M (1980) Mechanisms of action of antifungal drugs with special reference to the imidazole derivatives. Rev Infect Dis 2: 520–534

    Google Scholar 

  20. Van den Bossche H, Willemsens G, Cools W, Cornelissen F, Lauwers W, Van Cutsem J (1980) In vitro and in vivo effects of the antimycotic drug ketoconazole on sterol synthesis. Antimicrob Agents Chemother 17: 922–928

    Google Scholar 

  21. Rosenblatt H, Byrne W, Ament ME, Stiehm ER (1980) Successful treatment of chronic mucocutaneous candidiasis with ketoconazole. J Pediatr 97: 657–660

    Google Scholar 

  22. Brugmans J, Scheijgrond H, Van Cutsem J, Van den Bossche H, Baisier A, Hörig Ch (1980) Orale Langzeitbehandlung von Onychomycosen mit Ketoconazol. Mykosen 23: 405–415

    Google Scholar 

  23. Willemsen G, Cools W, Van den Bossche H (1980) Effects of miconazole and ketoconazole on sterol synthesis in a subcellular fraction of yeast and mammalian cells. In: Van den Bossche H (ed) The host invader interplay. Elsevier/North-Holland, Amsterdam, pp 691–694

    Google Scholar 

  24. Loose DS, Kan PB, Hirst MA, Marcus RA, Feldman D (1983) Ketoconazole blocks adrenal steroidogenesis by inhibiting cytochrome P450-dependent enzymes. J Clin Invest 71: 1495–1499

    Google Scholar 

  25. Santen RI, Van den Bossche H, Symoens J, Brugmans J, DeCoster R (1984) Site of action of low dose ketoconazole on androgen biosynthesis in men. J Clin Endocrinol Metab 57: 732–736

    Google Scholar 

  26. Hedstrand H (1975) A study of middle-aged men with particular reference to risk factors for cardiovascular disease. Uppsala J Med Sci [Suppl 19], p 26

    Google Scholar 

  27. Nikkilä EA, Kaste M, Ehnholm C, Viikari I (1978) Increase in serum high density lipoprotein in phenytoin users. Br Med J 2: 99

    Google Scholar 

  28. Luoma PV, Sotaniemi EA, Pelkonen RO, Ehnholm C (1982) High-density lipoproteins and hepatic microsomal enzyme induction in alcohol consumers. Res Commun Chem Pathol Pharm Ther 37: 91–96

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Dermatology, University of Uppsala, Uppsala, Sweden

    O. Rollman, S. Jameson & H. Lithell

  2. Department of Internal Medicine, University of Uppsala, Uppsala, Sweden

    S. Jameson

  3. Department of Geriatrics, University of Uppsala, Uppsala, Sweden

    H. Lithell

Authors
  1. O. Rollman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Jameson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. Lithell
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rollman, O., Jameson, S. & Lithell, H. Effects of long-term ketoconazole therapy on serum lipid levels. Eur J Clin Pharmacol 29, 241–245 (1985). https://doi.org/10.1007/BF00547430

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00547430

Key words

Search

Navigation