Itraconazole, a P-glycoprotein and CYP3A4 inhibitor, markedly raises the plasma concentrations and enhances the renin-inhibiting effect of aliskiren

Journal of Clinical Pharmacology

Volumn 51, Issue 3, 2011, Pages 359-367

  Tapaninen, Tuija ^a   Backman, Janne T ^a   Kurkinen, Kaisa J ^a   Neuvonen, Pertti J ^a   Niemi, Mikko ^a  

^a UNIVERSITY OF HELSINKI   (Finland)

Author keywords

aliskiren; drug interaction; itraconazole; Multidrug resistance transporter 1 P glycoprotein; pharmacokinetics

Indexed keywords

ALISKIREN; CYTOCHROME P450 3A4; GLYCOPROTEIN P; HYDROXYITRACONAZOLE; ITRACONAZOLE; PLACEBO; RENIN;

ADULT; AREA UNDER THE CURVE; ARTICLE; BLOOD PRESSURE MONITORING; CONTROLLED STUDY; CROSSOVER PROCEDURE; DIASTOLIC BLOOD PRESSURE; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG ELIMINATION; DRUG HALF LIFE; FEMALE; HEART RATE; HUMAN; HUMAN EXPERIMENT; KIDNEY CLEARANCE; MALE; MAXIMUM PLASMA CONCENTRATION; NORMAL HUMAN; PLASMA RENIN ACTIVITY; RANDOMIZED CONTROLLED TRIAL; SINGLE DRUG DOSE; SYSTOLIC BLOOD PRESSURE;

ADULT; AMIDES; ANTIFUNGAL AGENTS; ANTIHYPERTENSIVE AGENTS; BIOTRANSFORMATION; CROSS-OVER STUDIES; CYTOCHROME P-450 CYP3A; DRUG INTERACTIONS; ENZYME INHIBITORS; FEMALE; FUMARATES; HALF-LIFE; HUMANS; ITRACONAZOLE; MALE; METABOLIC CLEARANCE RATE; P-GLYCOPROTEIN; RENIN; YOUNG ADULT;

EID: 79953805995     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1177/0091270010365885     Document Type: Article

References (46)

1. Wood JM, Maibaum J, Rahuel J, et al. Structure-based design of aliskiren, a novel orally effective renin inhibitor. Biochem Biophys Res Commun. 2003;308:698-705. (Pubitemid 36976519)
2. Skeggs LT Jr, Kahn JR, Lentz K, Shumway NP. The preparation, purification, and amino acid sequence of a polypeptide renin substrate. J Exp Med. 1957;106:439-453.
3. Vaidyanathan S, Jarugula V, Dieterich HA, Howard D, Dole WP. Clinical pharmacokinetics and pharmacodynamics of aliskiren. Clin Pharmacokinet. 2008;47:515-531. (Pubitemid 351969826)
4. Vaidyanathan S, Jermany J, Yeh C, Bizot MN, Camisasca R. Aliskiren, a novel orally effective renin inhibitor, exhibits similar pharmacokinetics and pharmacodynamics in Japanese and Caucasian subjects. Br J Clin Pharmacol. 2006;62:690-698. (Pubitemid 44749546)
5. Waldmeier F, Glaenzel U, Wirz B, et al. Absorption, distribution, metabolism, and elimination of the direct renin inhibitor aliskiren in healthy volunteers. Drug Metab Dispos. 2007;35:1418-1428. (Pubitemid 47121784)
6. Shugarts S, Benet LZ. The role of transporters in the pharmacokinetics of orally administered drugs. Pharm Res. 2009;26:2039-2054.
7. Vaidyanathan S, Camenisch G, Schuetz H, et al. Pharmacokinetics of the oral direct renin inhibitor aliskiren in combination with digoxin, atorvastatin, and ketoconazole in healthy subjects: the role of P-glycoprotein in the disposition of aliskiren. J Clin Pharmacol. 2008;48:1323-1338.
8. Fromm MF. Importance of P-glycoprotein at blood-tissue barriers. Trends Pharmacol Sci. 2004;25:423-429. (Pubitemid 38981558)
9. Jurima-Romet M, Crawford K, Cyr T, Inaba T. Terfenadine metabolism in human liver: in vitro inhibition by macrolide antibiotics and azole antifungals. Drug Metab Dispos. 1994;22:849-857. (Pubitemid 24377359)
10. Olkkola KT, Backman JT, Neuvonen PJ. Midazolam should be avoided in patients receiving the systemic antimycotics ketoconazole or itraconazole. Clin Pharmacol Ther. 1994;55:481-485. (Pubitemid 24192233)
11. Wang EJ, Lew K, Casciano CN, Clement RP, Johnson WW. Interaction of common azole antifungals with P glycoprotein. Antimicrob Agents Chemother. 2002;46:160-165. (Pubitemid 34031618)
12. Marzolini C, Paus E, Buclin T, Kim RB. Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin Pharmacol Ther. 2004;75:13-33. (Pubitemid 38130115)
13. Neuvonen PJ, Niemi M, Backman JT. Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther. 2006;80:565-581. (Pubitemid 44908269)
14. Rao US, Scarborough GA. Direct demonstration of high affinity interactions of immunosuppressant drugs with the drug binding site of the human P-glycoprotein. Mol Pharmacol. 1994;45:773-776. (Pubitemid 24139207)
15. Kajosaari LI, Niemi M, Neuvonen M, Laitila J, Neuvonen PJ, Backman JT. Cyclosporine markedly raises the plasma concentrations of repaglinide. Clin Pharmacol Ther. 2005;78:388-399. (Pubitemid 41393674)
16. Ho RH, Tirona RG, Leake BF, et al. Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Gastroenterology. 2006;130:1793-1806.
17. European Public Assessment Report for Rasilez. URL:http://www.emea. europa.eu/humandocs/Humans/EPAR/rasilez/rasilez.htm. Accessed August 20, 2009.
18. Tekturna [prescribing information]. URL:http://www.pharma.us.novartis. com/product/pi/pdf/tekturna.pdf. Accessed August 20, 2009.
19. Jalava KM, Partanen J, Neuvonen PJ. Itraconazole decreases renal clearance of digoxin. Ther Drug Monit. 1997;19:609-613. (Pubitemid 28046984)
20. Templeton IE, Thummel KE, Kharasch ED, et al. Contribution of itraconazole metabolites to inhibition of CYP3A4 in vivo. Clin Pharmacol Ther. 2008;83:77-85.
21. Dresser GK, Spence JD, Bailey DG. Pharmacokineticpharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet. 2000;38:41-57. (Pubitemid 30055093)
22. Remmel RP, Dombrovskis D, Canafax DM. Assay of itraconazole in leukemic patient plasma by reversed-phase small-bore liquid chromatography. J Chromatogr. 1988;432:388-394.
23. Allenmark S, Edebo A, Lindgren K. Determination of itraconazole in serum with high-performance liquid chromatography and fluorescence detection. J Chromatogr. 1990;532:203-206. (Pubitemid 20349475)
24. Jaakkola T, Backman JT, Neuvonen M, Neuvonen PJ. Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics of pioglitazone. Clin Pharmacol Ther. 2005;77:404-414. (Pubitemid 40719268)
25. Niemi M, Tornio A, Pasanen MK, Fredrikson H, Neuvonen PJ, Backman JT. Itraconazole, gemfibrozil and their combination markedly raise the plasma concentrations of loperamide. Eur J Clin Pharmacol. 2006;62:463-472. (Pubitemid 43873718)
26. Azizi M, Webb R, Nussberger J, Hollenberg NK. Renin inhibition with aliskiren: where are we now, and where are we going? J Hypertens. 2006;24:243-256.
27. Kivistö KT, Niemi M, Fromm MF. Functional interaction of intestinal CYP3A4 and P-glycoprotein. Fundam Clin Pharmacol. 2004;18:621-626. (Pubitemid 39564261)
28. Back DJ, Tjia JF. Comparative effects of the antimycotic drugs ketoconazole, fluconazole, itraconazole and terbinafine on the metabolism of cyclosporin by human liver microsomes. Br J Clin Pharmacol. 1991;32:624-626.
29. von Moltke LL, Greenblatt DJ, Schmider J, et al. Midazolam hydroxylation by human liver microsomes in vitro: inhibition by fluoxetine, norfluoxetine, and by azole antifungal agents. J Clin Pharmacol. 1996;36:783-791. (Pubitemid 26329500)
30. von Moltke LL, Greenblatt DJ, Duan SX, Harmatz JS, Wright CE, Shader RI. Inhibition of terfenadine metabolism in vitro by azole antifungal agents and by selective serotonin reuptake inhibitor antidepressants: relation to pharmacokinetic interactions in vivo. J Clin Psychopharmacol. 1996;16:104-112.
31. Venkatakrishnan K, von Moltke LL, Greenblatt DJ. Effects of the antifungal agents on oxidative drug metabolism: clinical relevance. Clin Pharmacokinet. 2000;38:111-180. (Pubitemid 30122116)
32. Kim RB, Wandel C, Leake B, et al. Interrelationship between substrates and inhibitors of human CYP3A and P-glycoprotein. Pharm Res. 1999;16:408-414. (Pubitemid 29162099)
33. Shon JH, Yoon YR, Hong WS, et al. Effect of itraconazole on the pharmacokinetics and pharmacodynamics of fexofenadine in relation to the MDR1 genetic polymorphism. Clin Pharmacol Ther. 2005;78:191-201.
34. Allegra [prescribing information]. URL:http://products.sanofiaventis.us/ allegra/allegra.html. Accessed August 20, 2009.
35. Zhao P, Ragueneau-Majlessi I, Zhang L, et al. Quantitative evaluation of pharmacokinetic inhibition of CYP3A substrates by ketoconazole: a simulation study. J Clin Pharmacol. 2009;49:351-359.
36. Palkama VJ, Ahonen J, Neuvonen PJ, Olkkola KT. Effect of saquinavir on the pharmacokinetics and pharmacodynamics of oral and intravenous midazolam. Clin Pharmacol Ther. 1999;66:33-39. (Pubitemid 29350443)
37. Ho RH, Kim RB. Transporters and drug therapy: implications for drug disposition and disease. Clin Pharmacol Ther. 2005;78:260-277. (Pubitemid 41254111)
38. Becquemont L, Neuvonen M, Verstuyft C, et al. Amiodarone interacts with simvastatin but not with pravastatin disposition kinetics. Clin Pharmacol Ther. 2007;81:679-684. (Pubitemid 46625102)
39. Fenner KS, Troutman MD, Kempshall S, et al. Drug-drug interactions mediated through P-glycoprotein: clinical relevance and in vitro-in vivo correlation using digoxin as a probe drug. Clin Pharmacol Ther. 2009;85:173-181.
40. Hoffmeyer S, Burk O, von Richter O, et al. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci USA. 2000;97:3473-3478. (Pubitemid 30183327)
41. von Richter O, Burk O, Fromm MF, Thon KP, Eichelbaum M, Kivistö KT. Cytochrome P450 3A4 and P-glycoprotein expression in human small intestinal enterocytes and hepatocytes: a comparative analysis in paired tissue specimens. Clin Pharmacol Ther. 2004;75:172-183. (Pubitemid 38314866)
42. Thörn M, Finnström N, Lundgren S, Rane A, Lööf L. Cytochromes P450 and MDR1 mRNA expression along the human gastrointestinal tract. Br J Clin Pharmacol. 2005;60:54-60. (Pubitemid 40942781)
43. Vaidyanathan S, Reynolds C, Yeh CM, et al. Pharmacokinetics, safety, and tolerability of the novel oral direct renin inhibitor aliskiren in elderly healthy subjects. J Clin Pharmacol. 2007;47:453-460. (Pubitemid 46465958)
44. Gradman AH, Schmieder RE, Lins RL, Nussberger J, Chiang Y, Bedigian MP. Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients. Circulation. 2005;111:1012-1018. (Pubitemid 40354519)
45. Eyal S, Hsiao P, Unadkat JD. Drug interactions at the blood-brain barrier: fact or fantasy? Pharmacol Ther. 2009;123:80-104.
46. Schinkel AH, Mayer U, Wagenaar E, et al. Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drugtransporting) P-glycoproteins. Proc Natl Acad Sci USA. 1997;94:4028-4033. (Pubitemid 27180493)