Skip to main content
NCBI home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1993 Feb;35(2):156–160.

A study of the interaction between omeprazole and cyclosporine in renal transplant patients.

I Blohmé 1, J P Idström 1, T Andersson 1
PMCID: PMC1381507  PMID: 8443034

Abstract

1. To determine any interaction between omeprazole and cyclosporine A (CsA) 10 male patients with 1-7 year renal transplants and stable renal function, participated in this randomised blind cross-over trial with omeprazole, 20 mg, and placebo treatment once daily for 2 consecutive weeks each. 2. Blood samples for measurement of trough concentrations of CsA were obtained twice a week during the 4 study weeks, and during the 2 weeks before and after the study. Unchanged CsA concentrations were measured by h.p.l.c. and using a monoclonal antibody r.i.a., and drug plus metabolites were measured by a polyclonal antibody f.p.i.a. In addition, one of the metabolites, M17, was assayed separately by h.p.l.c. 3. The mean whole blood trough CsA concentration during omeprazole treatment was 102 (95% confidence interval, 84-122) micrograms l-1 determined by h.p.l.c. and 81 (65-100) micrograms l-1 determined by r.i.a. Corresponding values during placebo treatment were 100 (79-127) micrograms l-1 and 95 (75-120) micrograms l-1. The ratios between omeprazole and placebo treatments were 1.01 (0.84-1.22) (h.p.l.c.) and 0.85 (0.67-1.08) (r.i.a.). Assuming that a change of < 30% in CsA blood concentrations is of no clinical significance, these results show that there was no clinically or statistically significant influence of omeprazole on CsA concentrations. Neither CsA concentrations determined by f.p.i.a. nor determination of M17 by h.p.l.c. indicated any effect of omeprazole on the metabolism of CsA. 4. It is concluded that omeprazole (20 mg daily) does not significantly interfere with CsA metabolism in stabilised renal transplant patients and may be used safely without extra monitoring of blood CsA concentrations.

Full text

PDF
156

Selected References

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

  1. Ahonen J., Paimela H., Kauste A., Häyry P., Eklund B., Pettersson E. Ranitidine and cimetidine in renal transplantation: a clinical trial. Int J Tissue React. 1983;5(4):373–378. [PubMed] [Google Scholar]
  2. Andersson T. Omeprazole drug interaction studies. Clin Pharmacokinet. 1991 Sep;21(3):195–212. doi: 10.2165/00003088-199121030-00004. [DOI] [PubMed] [Google Scholar]
  3. Andersson T., Regårdh C. G., Dahl-Puustinen M. L., Bertilsson L. Slow omeprazole metabolizers are also poor S-mephenytoin hydroxylators. Ther Drug Monit. 1990 Jul;12(4):415–416. doi: 10.1097/00007691-199007000-00020. [DOI] [PubMed] [Google Scholar]
  4. Aoyama T., Yamano S., Waxman D. J., Lapenson D. P., Meyer U. A., Fischer V., Tyndale R., Inaba T., Kalow W., Gelboin H. V. Cytochrome P-450 hPCN3, a novel cytochrome P-450 IIIA gene product that is differentially expressed in adult human liver. cDNA and deduced amino acid sequence and distinct specificities of cDNA-expressed hPCN1 and hPCN3 for the metabolism of steroid hormones and cyclosporine. J Biol Chem. 1989 Jun 25;264(18):10388–10395. [PubMed] [Google Scholar]
  5. Badger A. M., Young J., Poste G. Reversal of histamine-mediated immunosuppression by structurally diverse histamine type II (H2) receptor antagonists. Int J Immunopharmacol. 1984;6(5):467–473. doi: 10.1016/0192-0561(84)90085-7. [DOI] [PubMed] [Google Scholar]
  6. Bargetzi M. J., Aoyama T., Gonzalez F. J., Meyer U. A. Lidocaine metabolism in human liver microsomes by cytochrome P450IIIA4. Clin Pharmacol Ther. 1989 Nov;46(5):521–527. doi: 10.1038/clpt.1989.180. [DOI] [PubMed] [Google Scholar]
  7. Bertilsson L., Henthorn T. K., Sanz E., Tybring G., Säwe J., Villén T. Importance of genetic factors in the regulation of diazepam metabolism: relationship to S-mephenytoin, but not debrisoquin, hydroxylation phenotype. Clin Pharmacol Ther. 1989 Apr;45(4):348–355. doi: 10.1038/clpt.1989.40. [DOI] [PubMed] [Google Scholar]
  8. Ged C., Rouillon J. M., Pichard L., Combalbert J., Bressot N., Bories P., Michel H., Beaune P., Maurel P. The increase in urinary excretion of 6 beta-hydroxycortisol as a marker of human hepatic cytochrome P450IIIA induction. Br J Clin Pharmacol. 1989 Oct;28(4):373–387. doi: 10.1111/j.1365-2125.1989.tb03516.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Guengerich F. P., Müller-Enoch D., Blair I. A. Oxidation of quinidine by human liver cytochrome P-450. Mol Pharmacol. 1986 Sep;30(3):287–295. [PubMed] [Google Scholar]
  10. Guengerich F. P. Oxidation of 17 alpha-ethynylestradiol by human liver cytochrome P-450. Mol Pharmacol. 1988 May;33(5):500–508. [PubMed] [Google Scholar]
  11. Jarowenko M. V., Van Buren C. T., Kramer W. G., Lorber M. I., Flechner S. M., Kahan B. D. Ranitidine, cimetidine, and the cyclosporine-treated recipient. Transplantation. 1986 Sep;42(3):311–312. doi: 10.1097/00007890-198609000-00018. [DOI] [PubMed] [Google Scholar]
  12. Klintmalm G., Säwe J., Ringdén O., von Bahr C., Magnusson A. Cyclosporine plasma levels in renal transplant patients. Association with renal toxicity and allograft rejection. Transplantation. 1985 Feb;39(2):132–137. doi: 10.1097/00007890-198502000-00005. [DOI] [PubMed] [Google Scholar]
  13. Kronbach T., Fischer V., Meyer U. A. Cyclosporine metabolism in human liver: identification of a cytochrome P-450III gene family as the major cyclosporine-metabolizing enzyme explains interactions of cyclosporine with other drugs. Clin Pharmacol Ther. 1988 Jun;43(6):630–635. doi: 10.1038/clpt.1988.87. [DOI] [PubMed] [Google Scholar]
  14. Kronbach T., Mathys D., Umeno M., Gonzalez F. J., Meyer U. A. Oxidation of midazolam and triazolam by human liver cytochrome P450IIIA4. Mol Pharmacol. 1989 Jul;36(1):89–96. [PubMed] [Google Scholar]
  15. Larsson R., Bodemar G., Kågedal B., Walan A. The effects of cimetidine (Tagamet) on renal function in patients with renal failure. Acta Med Scand. 1980;208(1-2):27–31. doi: 10.1111/j.0954-6820.1980.tb01145.x. [DOI] [PubMed] [Google Scholar]
  16. Lindholm A., Henricsson S., Lind M., Dahlqvist R. Intraindividual variability in the relative systemic availability of cyclosporin after oral dosing. Eur J Clin Pharmacol. 1988;34(5):461–464. doi: 10.1007/BF01046702. [DOI] [PubMed] [Google Scholar]
  17. Milito G., Taccone-Gallucci M., Brancaleone C., Nardi F., Filingeri V., Cesca D., Casciani C. U. Assessment of the upper gastrointestinal tract in hemodialysis patients awaiting renal transplantation. Am J Gastroenterol. 1983 Jun;78(6):328–331. [PubMed] [Google Scholar]
  18. Pachon J., Lorber M. I., Bia M. J. Effects of H2-receptor antagonists on renal function in cyclosporine-treated renal transplant patients. Transplantation. 1989 Feb;47(2):254–259. doi: 10.1097/00007890-198902000-00011. [DOI] [PubMed] [Google Scholar]
  19. Pichard L., Gillet G., Fabre I., Dalet-Beluche I., Bonfils C., Thenot J. P., Maurel P. Identification of the rabbit and human cytochromes P-450IIIA as the major enzymes involved in the N-demethylation of diltiazem. Drug Metab Dispos. 1990 Sep-Oct;18(5):711–719. [PubMed] [Google Scholar]
  20. Ptachcinski R. J., Venkataramanan R., Rosenthal J. T., Burckart G. J., Taylor R. J., Hakala T. R. Cyclosporine kinetics in renal transplantation. Clin Pharmacol Ther. 1985 Sep;38(3):296–300. doi: 10.1038/clpt.1985.174. [DOI] [PubMed] [Google Scholar]
  21. Romkes M., Faletto M. B., Blaisdell J. A., Raucy J. L., Goldstein J. A. Cloning and expression of complementary DNAs for multiple members of the human cytochrome P450IIC subfamily. Biochemistry. 1991 Apr 2;30(13):3247–3255. doi: 10.1021/bi00227a012. [DOI] [PubMed] [Google Scholar]
  22. Schnaper H. W., Aune T. M., Roby R. K. A role for histamine type II (H-2) receptor binding in production of the lymphokine, soluble immune response suppressor (SIRS). J Immunol. 1987 Aug 15;139(4):1185–1190. [PubMed] [Google Scholar]
  23. Shah A. K., Sawchuk R. J. Improved liquid-chromatographic determination of cyclosporine and its metabolites in blood. Clin Chem. 1988 Jul;34(7):1467–1471. [PubMed] [Google Scholar]
  24. Steger A. C., Timoney A. S., Griffen S., Salem R. R., Williams G. The influence of immunosuppression on peptic ulceration following renal transplantation and the role of endoscopy. Nephrol Dial Transplant. 1990;5(4):289–292. doi: 10.1093/ndt/5.4.289. [DOI] [PubMed] [Google Scholar]
  25. Uhlschmid G., Largiadèr F. Surgical prophylaxis of gastroduodenal complications associated with renal allotransplantation. World J Surg. 1977 May;1(3):397–405. doi: 10.1007/BF01556873. [DOI] [PubMed] [Google Scholar]
  26. Wadhwa N. K., Schroeder T. J., Pesce A. J., Myre S. A., Clardy C. W., First M. R. Cyclosporine drug interactions: a review. Ther Drug Monit. 1987 Dec;9(4):399–406. doi: 10.1097/00007691-198712000-00007. [DOI] [PubMed] [Google Scholar]
  27. Wallmark B., Lorentzon P., Larsson H. The mechanism of action of omeprazole--a survey of its inhibitory actions in vitro. Scand J Gastroenterol Suppl. 1985;108:37–51. [PubMed] [Google Scholar]
  28. Watkins P. B., Wrighton S. A., Maurel P., Schuetz E. G., Mendez-Picon G., Parker G. A., Guzelian P. S. Identification of an inducible form of cytochrome P-450 in human liver. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6310–6314. doi: 10.1073/pnas.82.18.6310. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES