Advertisement

Klinische Wochenschrift

, Volume 66, Issue 23, pp 1184–1189 | Cite as

Einfluß von Enalapril, Furosemid und Verapamil auf die Ciclosporin-Konzentration im Vollblut

  • Ch. H. Spes
  • Ch. E. Angermann
  • M. Anthuber
  • B. M. Kemkes
  • K. Theisen
Originalien

Abkürzungsverzeichnis

Harnstoff-N

Harnstoff-Stickstoff

GOT

Glutamat-Oxalazetat-Transaminase

GPT

Glutamat-Pyruvat-Transaminase

APH

Alkalische Phosphatase

GammaGT

Gamma-Glutamyl-Transferase

CHE

Cholinesterase

RIA

Radio-Immuno-Assay

Influence of enalapril, furosemide and verapamil on ciclosporin whole blood levels

Summary

Introduction of ciclosporin A into immunosuppressive therapy is considered a major progress in improving results of organ transplantation. Clinical use of ciclosporin, however, is limited by a low therapeutic index and toxic side effects. Therefore, interactions of ciclosporin with other drugs are clinically important. In our study, we used enalapril, furosemide and verapamil for treatment of arterial hypertension in cardiac transplant recipients and investigated the influence of these drugs on ciclosporin whole blood trough levels. The antihypertensive regimen used in this study normalized blood pressure in each of the 25 patients. Enalapril and furosemide did not influence ciclosporin levels. Adding verapamil, however, resulted in a significant increase of ciclosporin levels, whereas cessation of the drug in one patient treated with verapamil only lowered ciclosporin levels. Thus, when verapamil is introduced or discontinued in patients on ciclosporin, close monitoring of ciclosporin levels and dosage adjustment are necessary. Besides its specific effects verapamil allows reduction of ciclosporin dosage necessary to maintain unaltered levels, which is important regarding cost of therapy. In general, use of any drug with unknown influence on ciclosporin levels requires careful monitoring, even if information exists on other substances of the same group of drugs in this respect. This is especially indicated in drugs known to influence the hepatic cytochrome P450 enzyme system.

Key words

Ciclosporin Enalapril Furosemide Verapamil Pharmacological interaction Heart transplantation 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  1. 1.
    Bourbigot B, Guiserix J, Airiau J, Ressollette L, Morin JF, Cledes J (1986) Nicardipine increases cyclosporin blood levels. Lancet I:1447Google Scholar
  2. 2.
    Burke MD, Whiting PH (1986) The role of drug metabolism in cyclosporine A nephrotoxicity. Clin Nephrol 25:111–116Google Scholar
  3. 3.
    Chapman JR, Griffiths D, Harding NGL, Morris PJ (1985) Reversibility of cyclosporin nephrotoxicity after three months' treatment. Lancet I:128–130Google Scholar
  4. 4.
    Cockburn I (1986) Cyclosporine A: A clinical evaluation of drug interactions. Transplant Proc 18:Suppl. 5:50–55Google Scholar
  5. 5.
    Evans RW, Manninen DL (1987) Cost of cyclosporin. Lancet II:1472Google Scholar
  6. 6.
    Evans RW, Manninen DL (1988) Economic impact of cyclosporine in transplantation. Transplant Proc (in press)Google Scholar
  7. 7.
    Graffenried B von, Krupp P (1985) Nebenwirkungen von Ciclosporin nach Nierentransplantation und bei Autoimmunerkrankungen. Internist 26:542–548Google Scholar
  8. 8.
    Irschik E, Tilg H, Niederwieser D, Gastl G, Huber Ch, Margreiter M (1984) Cyclosporin blood levels do correlate with clinical complications. Lancet II:692–693Google Scholar
  9. 9.
    Kahan BD (1987) Immunosuppressive therapy with cyclosporine for cardic transplantation. Circulation 75:40–56Google Scholar
  10. 10.
    Kaye MP (1987) The registry of the International Society for Heart Transplantation: Fourth official report — 1987. J Heart Transplant 6:63–67Google Scholar
  11. 11.
    Lemaire M, Maurer G, Wood AJ (1986) Ciclosporin: Pharmacokinetics and metabolism. Prog Allergy 38:93–107Google Scholar
  12. 12.
    Lindholm A, Henricsson S (1987) Verapamil inhibits cyclosporin metabolism. Lancet I:1262–1263Google Scholar
  13. 13.
    Myers BD, Ross J, Newton L, Luetscher J, Perlroth M (1984) Cyclosporine-associated chronic nephropathy. N Engl J Med 311:669–705Google Scholar
  14. 14.
    Pochet JM, Pirson Y (1986) Cyclosporin-diltiazem interaction. Lancet I:979Google Scholar
  15. 15.
    Ptachcinsky RJ, Carpenter BJ, Burckart GJ, Venkataramanan R, Rosenthal JT (1985) Effect of erythromycin on cyclosporine levels. N Engl J Med 313:1416–1417Google Scholar
  16. 16.
    Renton KW (1985) Inhibition of hepatic microsomal drug metabolism by the calcium channel blockers diltiazem and verapamil. Biochem Pharmacol 34:2549–2553Google Scholar
  17. 17.
    Rottembourg J, Mattei MF, Cabrol A, Leger P, Aupetit B, Beaufils H, Gluckman JC, Pavie A, Gandjbakhch I, Cabrol C (1985) Renal function and blood pressure in heart transplant recipients treated with cyclosporine. J Heart Transplant 4:404–408Google Scholar
  18. 18.
    Ryffel B, Siegl H, Petric R, Muller AM, Hauser R, Mihatsch MJ (1986) Nephrotoxicity of cyclosporine in spontaneously hypertensive rats: effects on blood pressure and vascular lesions. Clin Nephrol 25:Suppl 1:193–198Google Scholar
  19. 19.
    Spes CH, Angermann CE, Zellner M, Anthuber M, Kemkes BM, Theisen K (1987) Einfluss von Enalapril, Furosemid und Verapamil auf den Ciclosporinspiegel nach orthotoper Herztransplantation. Z Kardiol 76:Suppl.3:37Google Scholar
  20. 20.
    Spratt P, Esmore D, Baron D, Shanahan MX, Farnsworth AE, Chang VP (1987) Effects of low-dose cyclosporine A on toxicity and rejection in cardiac transplantation. Transplant Proc 19:2847–2850Google Scholar
  21. 21.
    Thompson ME, Shapiro AP, Johnsen AM, Reeves R, Itzkoff J, Ginchereau E, Hardesty RL, Griffith BL, Bahnson HT, McDonald R Jr (1983) New onset of hypertension following cardiac transplantation: A preliminary report and analysis. Transplant Proc 15:Suppl. 1:2573–2577Google Scholar
  22. 22.
    Uchida K, Orihara A, Tominaga Y, Yamada N, Nakanishi N, Kawai M, Kondo T, Akaza T, Morozumi K, Morimoto T, Kano T, Takagi H (1987) Correlation between whole blood and plasma cyclosporine levels. Transplant Proc 19:1764–1768Google Scholar
  23. 23.
    Whiting PH, Cunningham C, Thompson AW, Simpson JG (1984) Enhancement of high dose cyclosporin A toxicity by frusemide. Biochem Pharmacol 33:1075–1079Google Scholar
  24. 24.
    Whiting PH, Burke MD, Thompson AW (1986) Drug interactions with cyclosporine: Implications from animal studies. Transplant Proc 18:Suppl. 5:56–70Google Scholar
  25. 25.
    Wonigeit K (1985) Pharmakokinetik von Ciclosporin A und Bedeutung der Blutspiegelmessung für die Therapie. Internist 26:534–542Google Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • Ch. H. Spes
    • 1
  • Ch. E. Angermann
    • 1
  • M. Anthuber
    • 2
  • B. M. Kemkes
    • 2
  • K. Theisen
    • 1
  1. 1.Medizinische Klinik InnenstadtUniversität MünchenGermany
  2. 2.Herzchirurgische Klinik, Klinikum GroßhadernUniversität MünchenGermany

Personalised recommendations