Pharmacokinetic and pharmacodynamic interactions between the immunosuppressant sirolimus and the lipid-lowering drug ezetimibe in healthy volunteers

Clinical Pharmacology and Therapeutics

Volumn 87, Issue 6, 2010, Pages 663-667

  Oswald, S ^a   Nassif, A ^a   Modess, C ^a   Keiser, M ^a   Hanke, U ^a   Engel, A ^a   Lutjohann D ^a   Weitschies, W ^a   Siegmund, W ^a  

^a UNIVERSITY OF GREIFSWALD   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

EZETIMIBE; MULTIDRUG RESISTANCE PROTEIN 1; ORGANIC ANION TRANSPORTER 2; PIMECROLIMUS; PROBENECID; RAPAMYCIN;

ADULT; ANIMAL CELL; AREA UNDER THE CURVE; ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG EXCRETION; EMBRYO; ENZYME ACTIVITY; ENZYME SPECIFICITY; FEMALE; GRAFT REJECTION; HUMAN; HUMAN CELL; IMMUNOSUPPRESSIVE TREATMENT; MALE; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; NORMAL HUMAN; PHARMACODYNAMICS; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION;

ADULT; ANIMALS; ANTICHOLESTEREMIC AGENTS; AZETIDINES; CELL LINE; CELLS, CULTURED; CROSS-OVER STUDIES; DOGS; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HUMANS; IMMUNOSUPPRESSIVE AGENTS; MALE; ORGANIC ANION TRANSPORTERS; SIROLIMUS; TRANSFECTION; YOUNG ADULT;

EID: 77952585564     PISSN: 00099236     EISSN: 15326535     Source Type: Journal    
DOI: 10.1038/clpt.2009.266     Document Type: Article

References (30)

1. Meier-Kriesche H.U., et al. Immunosuppression: evolution in practice and trends 1994-2004. Am. J. Transplant. 6;1111-1131 (2006).
2. Bilchick, K.C., Henrikson, C.A., Skojec, D., Kasper, E.K. & Blumenthal, R.S. Treatment of hyperlipidemia in cardiac transplant recipients. Am. Heart J. 148, 200-210 (2004).
3. Wiesbauer, F., Heinze, G., Mitterbauer, C., Harnoncourt, F., Hörl, W.H. & Oberbauer, R. Statin use is associated with prolonged survival of renal transplant recipients. J. Am. Soc. Nephrol. 19, 2211-2218 (2008)
4. Neuvonen, P.j., Niemi, M. & Backman, j.T. Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin. Pharmacol. Ther. 80, 565-581 (2006).
5. Buchanan, C., Smith, L., Corbett, j., Nelson, E. & Shihab, F. A retrospective analysis of ezetimibe treatment in renal transplant recipients. Am. J. Transplant. 6, 770-774 (2006).
6. Kohnle, M., Pietruck, F., Kribben, A., Philipp, T., Heemann, U. & Witzke, O. Ezetimibe for the treatment of uncontrolled hypercholesterolemia in patients with high-dose statin therapy after renal transplantation. Am. J. Transplant. 6, 205-208 (2006).
7. Almutairi, F., Peterson, T.C., Molinari, M., Walsh, M.j., Alwayn, I. & Peltekian, K.M. Safety and efectiveness of ezetimibe in liver transplant recipients with hypercholesterolemia. Liver Transpl. 15, 504-508 (2009).
8. Bergman, A.j. et al. Efects of ezetimibe on cyclosporine pharmacokinetics in healthy subjects. J. Clin. Pharmacol. 46, 321-327 (2006).
9. Koshman, S.L., Lalonde, L.D., Burton, I., Tymchak, W.j. & Pearson, G.j. Supratherapeutic response to ezetimibe administered with cyclosporine. Ann. Pharmacother. 39, 1561-1565 (2005). (Pubitemid 41197143)
10. Bergman, A.j. et al. Interaction of single-dose ezetimibe and steady-state cyclosporine in renal transplant patients. J. Clin. Pharmacol. 46, 328-336 (2006).
11. Kosoglou, T., Statkevich, P., johnson-Levonas, A.O., Paolini, j.F., Bergman, A.j. & Alton, K.B. Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin. Pharmacokinet. 44, 467-494 (2005).
12. Oswald, S. et al. Intestinal expression of P-glycoprotein (ABCB1), multidrug resistance associated protein 2 (ABCC2), and uridine diphosphate-glucuronosyltransferase 1A1 predicts the disposition and modulates the efects of the cholesterol absorption inhibitor ezetimibe in humans. Clin. Pharmacol. Ther. 79, 206-217 (2006).
13. Oswald, S. et al. Disposition of ezetimibe is infuenced by polymorphisms of the hepatic uptake carrier OATP1B1. Pharmacogenet. Genomics 18, 559-568 (2008).
14. Böhme, M., jedlitschky, G., Leier, I., Büchler, M. & Keppler, D. ATP-dependent export pumps and their inhibition by cyclosporins. Adv. Enzyme Regul. 34, 371-380 (1994).
15. Fehrenbach, T., Cui, Y., Faulstich, H. & Keppler, D. Characterization of the transport of the bicyclic peptide phalloidin by human hepatic transport proteins. Naunyn Schmiedebergs Arch. Pharmacol. 368, 415-420 (2003).
16. Mahalati, K. & Kahan, B.D. Clinical pharmacokinetics of sirolimus. Clin. Pharmacokinet. 40, 573-585 (2001).
17. Picard, N., Prémaud, A., Rousseau, A., Le Meur, Y. & Marquet, P. A comparison of the efect of ciclosporin and sirolimus on the pharmokinetics of mycophenolate in renal transplant patients. Br. J. Clin. Pharmacol. 62, 477-484 (2006).
18. Fridell, j.A. et al. Phenytoin decreases the blood concentrations of sirolimus in a liver transplant recipient: a case report. Ther. Drug Monit. 25; 117-119 (2003).
19. Zimmerman, j.j. Exposure-response relationships and drug interactions of sirolimus. AAPS. J. 6, e28 (2004).
20. Puthenparumpil, j.j., Keough-Ryan, T., Kiberd, M., Lawen, j. & Kiberd, B.A. Treatment of hypercholesterolemia with ezetimibe in the kidney transplant population. Transplant. Proc. 37, 1033-1035 (2005).
21. Miettinen, T.A., Tilvis, R.S. & Kesäniemi, Y.A. Serum plant sterols and cholesterol precursors refect cholesterol absorption and synthesis in volunteers of a randomly selected male population. Am. J. Epidemiol. 131, 20-31 (1990).
22. Oswald, S. et al. Disposition and sterol-lowering efect of ezetimibe are infuenced by single-dose coadministration of rifampin, an inhibitor of multidrug transport proteins. Clin. Pharmacol. Ther. 80, 477-485 (2006).
23. Reihnér, E. et al. Infuence of pravastatin, a specifc inhibitor of HMG-CoA reductase, on hepatic metabolism of cholesterol. N. Engl. J. Med. 323, 224-228 (1990).
24. Reyderman, L., Kosoglou, T., Boutros, T., Seiberling, M. & Statkevich, P. Pharmacokinetic interaction between ezetimibe and lovastatin in healthy volunteers. Curr. Med. Res. Opin. 20, 1493-1500 (2004).
25. Cui, Y., König, j. & Keppler, D. Vectorial transport by double-transfected cells expressing the human uptake transporter SLC21A8 and the apical export pump ABCC2. Mol. Pharmacol. 60, 934-943 (2001).
26. Fardel, O., Lecureur, V., Loyer, P. & Guillouzo, A. Rifampicin enhances anti-cancer drug accumulation and activity in multidrug-resistant cells. Biochem. Pharmacol. 49, 1255-1260 (1995).
27. Vavricka, S.R., Van Montfoort, j., Ha, H.R., Meier, P.j. & Fattinger, K. Interactions of rifamycin SV and rifampicin with organic anion uptake systems of human liver. Hepatology. 36, 164-172 (2002).
28. Tirona, R.G., Leake, B.F., Wolkof, A.W. & Kim, R.B. Human organic anion transporting polypeptide-C (SLC21A6) is a major determinant of rifampin-mediated pregnane X receptor activation. J. Pharmacol. Exp. Ther. 304, 223-228 (2003).
29. Oswald, S., Sc, E., Cascorbi, I. & Siegmund, W. A LC-MS/MS method to quantify the novel cholesterol lowering drug ezetimibe in human serum, urine and feces in healthy subjects genotyped for SLCO1B1. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 830, 143-150 (2006).
30. Thelen, K.M., Laaksonen, R., Päivä, H., Lehtimäki, T. & Lütjohann, D. High-dose statin treatment does not alter plasma marker for brain cholesterol metabolism in patients with moderately elevated plasma cholesterol levels. J. Clin. Pharmacol. 46, 812-816 (2006).