Clinical pharmacodynamics and pharmacokinetics of the antifungal extended-spectrum triazole posaconazole: An overview

British Journal of Clinical Pharmacology

Volumn 70, Issue 4, 2010, Pages 471-480

  Lipp, Hans Peter ^a  

^a UNIVERSITY OF TÜBINGEN   (Germany)

Author keywords

drug interactions; oral bioavailability; posaconazole; review; therapeutic drug monitoring

Indexed keywords

ANTIARRHYTHMIC AGENT; ANTIFUNGAL AGENT; BUSULFAN; CALCIUM CHANNEL BLOCKING AGENT; CASPOFUNGIN; CIMETIDINE; CYCLOSPORIN; DOFETILIDE; EVEROLIMUS; FLUCONAZOLE; ITRACONAZOLE; KETOCONAZOLE; METOCLOPRAMIDE; MIDAZOLAM; OMEPRAZOLE; PHENYTOIN; POSACONAZOLE; QUINIDINE; RAPAMYCIN; RETINOIC ACID; RIFAMPICIN; SIMVASTATIN; TACROLIMUS; TRIAZOLE DERIVATIVE; VINCA ALKALOID; VORICONAZOLE;

ABDOMINAL PAIN; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANOREXIA; ANTIFUNGAL ACTIVITY; CLINICAL TRIAL; COCCIDIOIDOMYCOSIS; CRYPTOCOCCOSIS; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG ELIMINATION; DRUG METABOLISM; DRUG MONITORING; DRUG SAFETY; DRUG TOLERABILITY; ESOPHAGUS CANDIDIASIS; FOOD; FOOD DRUG INTERACTION; HEADACHE; HUMAN; INVASIVE ASPERGILLOSIS; INVASIVE CANDIDIASIS; MINIMUM INHIBITORY CONCENTRATION; NAUSEA; OROPHARYNX CANDIDIASIS; PHARMACODYNAMICS; PRIORITY JOURNAL; REVIEW; SIDE EFFECT; SYSTEMIC MYCOSIS; ZYGOMYCOSIS;

ANTIFUNGAL AGENTS; AREA UNDER CURVE; BIOLOGICAL AVAILABILITY; DRUG INTERACTIONS; DRUG RESISTANCE, FUNGAL; FUNGI; HUMANS; TRIAZOLES;

EID: 77956593204     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/j.1365-2125.2010.03680.x     Document Type: Review

References (67)

1. Nagappan V, Deresinski S. Posaconazole: a broad-spectrum triazole antifungal agent. Clin Infect Dis 2007 45:1610 1617.
2. Courtney R, Wexler D, Radwanski E, Lim J, Laughlin M. Effect of food on the relative bioavailability of two oral formulations of posaconazole in healthy adults. Br J Clin Pharmacol 2003 57:218 222.
3. Lipp HP. Antifungal agents - clinical pharmacokinetics and drug interactions. Mycoses 2008 51:7 18.
4. Schiller DS, Fung HB. Posaconazole: an extended-spectrum triazole antifungal agent. Clin Ther 2007 29:1862 1886.
5. Keating GM. Posaconazole. Drugs 2005 65:1553 1567.
6. Templeton IE, Thummel KE, Kharasch ED, Kunze KL, Hoffer C, Nelson WL, Isoherranen N. Contribution of itraconazole metabolites to inhibition of CYP3A4 in vivo. Clin Pharmacol Ther 2008 83:77 85.
7. Galetin A, Ito K, Hallifax D, Houston JB. CYP3A4 substrate selection and substitution in the prediction of potential drug-drug interactions. J Pharmacol Exp Ther 2005 314:180 190.
8. Jeong S, Nguyen PD, Desta Z. Comprehensive in vitro inhibition analysis of 8 cytochrome P450 (CYP) enzymes by voriconazole: major effect on CYPs 2B6, 2C9, 2C19 and 3A. Antimicrob Agents Chemother 2008 53:541 551.
9. Courtney R, Pai S, Laughlin M, Lim J, Batra V. Pharmacokinetics, safety, and tolerability of oral posaconazole administered in single and multiple doses in healthy adults. Antimicrob Agents Chemother 2003 47:2788 2795.
10. Krishna G, Martinho M, Chandrasekar P, Ullmann AJ, Patino H. Pharmacokinetics of oral posaconazole in allogeneic hematopoietic stem cell transplant recipients with graft-versus-host disease. Pharmacotherapy 2007 27:1627 1636.
11. Goodwin ML, Drew RH. Antifungal serum concentration monitoring: an update. J Antimicrob Chemother 2008 61:17 25.
12. Pfaller MA, Messer S, Jones RN. Activity of a new triazole, Sch 56592, compared with those of four other antifungal agents tested against clinical isolates of Candida spp. and Saccharomyces cerevisiae. Antimicrob Agents Chemother 1997 41:233 235.
13. Diekema DJ, Messer SA, Hollis RJ, Jones RN, Pfaller MA. Activities of caspofungin, itraconazole, posaconazole, ravuconazole, voriconazole, and amphotericin B against 448 recent clinical isolates of filamentous fungi. J Clin Microbiol 2003 41:3623 3626.
14. Barchiesi F, Schimizzi AM, Caselli F, Giannini D, Camiletti V, Fileni B, Giacometti A, Di Francesco LF, Scalise G. Activity of the new antifungal triazole, posaconazole, against Cryptococcus neoformans. J Antimicrob Chemother 2001 48:769 773. (Pubitemid 33735311)
15. Spreghini E, Maida CM, Milici ME, Scalise G, Barchiesi F. Posaconazole activity against Candida glabrata after exposure to caspofungin or amphotericin B. Antimicrob Agents Chemother 2008 52:513 517. (Pubitemid 351170822)
16. Sabatelli F, Patel R, Mann PA, Mendrick CA, Norris CC, Hare R, Loebenberg D, Black TA, McNicholas PM. In vitro activities of posaconazole, fluconazole, itraconazole, voriconazole, and amphotericin B against a large collection of clinically important molds and yeasts. Antimicrob Agents Chemother 2006 50:2009 2015.
17. Cacciapuoti A, Halpern J, Mendrick C, Norris C, Patel R, Loebenberg D. Interaction between posaconazole and caspofungin in concomitant treatment of mice with systemic Aspergillus infection. Antimicrob Agents Chemother 2006 50:2587 2590.
18. Guembe M, Guinea J, Pelaez T, Torres-Narbona M, Bouza E. Synergistic effect of posaconazole and caspofungin against clinical zygomycetes. Antimicrob Agents Chemother 2007 51:3457 3458.
19. Cuenca-Estrella M. Combinations of antifungal agents in therapy: what value are they? J Antimicrob Chemother 2004 54:854 869.
20. Krishna G, Tarif MA, Xuan F, Martinho M, Angulo D, Cornely OA. Pharmacokinetics of oral posaconazole in neutropenic patients receiving chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome. Pharmacotherapy 2008 28:1223 1232.
21. Ezzet F, Wexler D, Courtney R, Krishna G, Lim J, Laughlin M. Oral bioavailability of posaconazole in fasted healthy subjects: comparison between three regimens and basis for clinical dosage recommendations. Clin Pharmacokinet 2005 44:211 220.
22. Bruggemann RJM, Alffenaar JWC, Blijlevens NMA, Billaud EM, Kosterink JGW, Verweij PE, Burger DM. Clinical relevance of the pharmacokinetic interactions of azole antifungal drugs with other coadministered agents. Clin Infect Dis 2009 48:1441 1458.
23. Conte JE, Jr., Golden JA, Krishna G, McIver M, Little E, Zurlinden E. Intrapulmonary pharmacokinetics and pharmacodynamics of posaconazole at steady state in healthy subjects. Antimicrob Agents Chemother 2008 53:703 707.
24. Pitisuttithum P, Negroni R, Graybill JR, Bustamante B, Pappas P, Chapman S, Hare RS, Hardalo CJ. Activity of posaconazole in the treatment of central nervous system fungal infections. J Antimicrob Chemother 2005 56:745 755.
25. Ruping MJGT, Albermann N, Ebinger F, Burckhardt I, Beisel C, Muller C, Vehreschild JJ, Kochanek M, Fatkenheuer G, Bangard C, Ullmann AJ, Herr W, Kolbe K, Hallek M, Cornely OA. Posaconazole concentrations in the central nervous system. J Antimicrob Chemother 2008 62:1468 1470.
26. Sansone-Parsons A, Krishna G, Simon J, Soni P, Kantesaria B, Herron J, Stoltz R. Effects of age, gender, and race/ethnicity on the pharmacokinetics of posaconazole in healthy volunteers. Antimicrob Agents Chemother 2007 51:495 502.
27. Ghosal A, Hapangama N, Yuan Y, Achanfuo-Yeboah J, Iannucci R, Chowdhury S, Alton K, Patrick JE, Zbaida S. Identification of human UDP- glucuronosyltransferase enzyme(s) responsible for the glucuronidation of posaconazole (Noxafil). Drug Metab Dispos 2004 32:267 271. (Pubitemid 38176945)
28. Krieter P, Flannery B, Musick T, Gohdes M, Martinho M, Courtney R. Disposition of posaconazole following single-dose oral administration in healthy subjects. Antimicrob Agents Chemother 2004 48:3543 3551.
29. Krishna G, Sansone-Parsons A, Martinho M, Kantesaria B, Pedicone L. Posaconazole plasma concentrations in juvenile patients with invasive fungal infection. Antimicrob Agents Chemother 2007 51:812 818.
30. Courtney R, Sansone A, Smith W, Marbury T, Statkevich P, Martinho M, Laughlin M, Swan S. Posaconazole pharmacokinetics, safety, and tolerability in subjects with varying degrees of chronic renal disease. J Clin Pharmacol 2005 45:185 192.
31. Hachem RY, Langston AA, Graybill JR, Perfect JR, Pedicone LD, Patino H, Raad II. Posaconazole as salvage treatment of invasive fungal infections in patients with underlying renal impairment. J Antimicrob Chemother 2008 62:1386 1391 doi:10.1093/jac/dkn401.
32. Andes D, Pascual A, Marchetti O. Antifungal therapeutic drug monitoring: established and emerging indications. Antimicrob Agents Chemother 2009 53:24 34.
33. Moton A, Krishna G, Ma L, O'Mara E, Prasad P, McLeod J, Preston RA. Pharmacokinetics of a single dose of the antifungal posaconazole as oral suspension in subjects with hepatic impairment. Curr Med Res Opin 2009 26:1 7 doi:10.1185/03007990903364657.
34. Walsh TJ, Hiemenz JW, Seibel NL, Perfect JR, Horwith G, Lee L, Silber JL, DiNubile MJ, Reboli A, Bow E, Lister J, Anaissie EJ. Amphotericin B lipid complex for invasive fungal infections: analysis of safety and efficacy in 556 cases. Clin Infect Dis 1998 26:1383 1396.
35. Moton A, Krishna G, Wang Z. Tolerability and safety profile of posaconazole: evaluation of 18 controlled studies in healthy volunteers. J Clin Pharm Ther 2009 34:301 311.
36. Ullmann AJ, Cornely OA, Burchardt A, Hachem R, Kontoyiannis DP, Topelt K, Courtney R, Wexler D, Krishna G, Martinho M, Corcoran G, Raad I. Pharmacokinetics, safety, and efficacy of posaconazole in patients with persistent febrile neutropenia or refractory invasive fungal infection. Antimicrob Agents Chemother 2006 50:658 666.
37. Walsh TJ, Raad I, Patterson TF, Chandrasekar P, Donowitz GR, Graybill R, Greene RE, Hachem R, Hadley S, Herbrecht R, Langston A, Louie A, Ribaud P, Segal BH, Stevens DA, van Burik J-AH, White CS, Corcoran G, Gogate J, Krishna G, Pedicone L, Hardalo C, Perfect JR. Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: an externally controlled trial. Clin Infect Dis 2007 44:2 12.
38. Denning DW, Ribaud P, Milpied N, Caillot D, Herbrecht R, Thiel E, Haas A, Ruhnke M, Lode H. Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis. Clin Infect Dis 2002 34:563 571.
39. Kartsonis NA, Saah AJ, Joy Lipka C, Taylor AF, Sable CA. Salvage therapy with caspofungin for invasive aspergillosis: results from the caspofungin compassionate use study. J Infect 2005 50:196 205.
40. Ullmann AJ, Lipton JH, Vesole DH, Chandrasekar P, Langston A, Tarantolo SR, Greinix H, Morais de Azevedo W, Reddy V, Boparai N, Pedicone L, Patino H, Durrant S. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med 2007 356:335 347.
41. Cornely OA, Ullmann AJ. Numbers needed to treat with posaconazole prophylaxis to prevent invasive fungal infection and death. Clin Infect Dis 2008 46:1626 1627.
42. Cornely OA, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ, Helfgott D, Holowiecki J, Stockelberg D, Goh Y-T, Petrini M, Hardalo C, Suresh R, Angulo-Gonzalez D. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med 2007 356:348 359.
43. van Burik J-AH, Hare RS, Solomon HF, Corrado ML, Kontoyiannis DP. Posaconazole is effective as salvage therapy in zygomycosis: a retrospective summary of 91 cases. Clin Infect Dis 2006 42:e61 e65.
44. Vazquez JA, Skiest DJ, Nieto L, Northland R, Sanne I, Gogate J, Greaves W, Isaacs R. A multicenter, randomized trial evaluating posaconazole versus fluconazole for the treatment of oropharyngeal candidiasis in subjects with HIV/AIDS. Clin Infect Dis 2006 42:1179 1186.
45. Skiest DJ, Vazquez JA, Anstead GM, Graybill JR, Reynes J, Ward D, Hare R, Boparai N, Isaacs R. Posaconazole for the treatment of azole-refractory oropharyngeal and esophageal candidiasis in subjects with HIV infection. Clin Infect Dis 2007 44:607 614.
46. Groll AH. Slavage treatment with posaconazole in pediatric patients. Mycoses 2009 52.
47. Raad II, Graybill JR, Bustamante AB, Cornely OA, Gaona-flores V, Afif C, Graham DR, Greenberg RN, Hadley S, Langston A, Negroni R, Perfect JR, Pitisuttithum P, Restrepo A, Schiller G, Pedicone L, Ullmann AJ. Safety of long-term oral posaconazole use in the treatment of refractory invasive fungal infections. Clin Infect Dis 2006 42:1726 1734.
48. Courtney R, Radwanski E, Lim J, Laughlin M. Pharmacokinetics of posaconazole coadministered with antacid in fasting or nonfasting healthy men. Antimicrob Agents Chemother 2004 48:804 808.
49. Courtney R, Wexler D, Statkevich P, Lim J, Batra V, Laughlin M. Effect of cimetidine on the pharmacokinetics of posaconazole in healthy volunteers abstract. 9-27-2002. Thesis/Dissertation. Poster presented at: 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; September 27-30, 2002; San Diego, CA.
50. Krishna G, Moton A, Ma L, Medlock MM, McLeod J. The pharmacokinetics and absorption of posaconazole oral suspension under various gastric conditions in healthy volunteers. Antimicrob Agents Chemother 2009 53:958 966.
51. Alffenaar JW, van Assen S, van der Werf TS, Kosterink JG, Uges DR. Omeprazole significantly reduces posaconazole serum trough level. Clin Infect Dis 2009 48:839.
52. Wexler D, Courtney R, Richards W, Banfield C, Lim J, Laughlin M. Effect of posaconazole on cytochrome P450 enzymes: a randomized, open-label, two-way crossover study. Eur J Pharm Sci 2004 21:645 653.
53. Galetin A, Hinton LK, Burt H, Obach RS, Houston JB. Maximal inhibition of intestinal first-pass metabolism as a pragmatic indicator of intestinal contribution to the drug-drug interactions for CYP3A4 cleared drugs. Curr Drug Metab 2007 8:685 693.
54. Krishna G, Moton A, Ma L, Savant I, Martinho M, Seiberling M, McLeod J. Effects of oral posaconazole on the pharmacokinetic properties of oral and intravenous midazolam: a phase I, randomized, open-label, crossover study in healthy volunteers. Clin Ther 2009 31:286 298.
55. Huang SM, Temple R, Throckmorton DC, Lesko LJ. Drug interaction studies: study design, data analysis, and implications for dosing and labeling. Clin Pharmacol Ther 2007 81:298 304.
56. Merck & Co., Inc. Zocor® (Simvastatin) Tablets. Whitehouse Station, NJ:Merck & Co., Inc, 2005.
57. Sansone-Parsons A, Krishna G, Martinho M, Kantesaria B, Gelone S, Mant TG. Effect of oral posaconazole on the pharmacokinetics of cyclosporine and tacrolimus. Pharmacotherapy 2007 27:825 834.
58. Moton A, Ma L, Krishna G, Martinho M, Seiberling M, McLeod J. Effects of oral posaconazole on the pharmacokinetics of sirolimus. Curr Med Res Opin 2009 25:701 707.
59. Drew RH. Posaconazole in the treatment of selected IFIs. Hospital Pharmacy 2006 34 9.
60. SP Europe. Noxafil 40 mg/Ml Oral Suspension Summary of Product Characteristics Brussels, Belgium:SP Europe, 2007.
61. Spriet I, Meersseman W, Wilmer WS, Willems HJ, Krishna A. Mini-series: II. Clinical aspects. Clinically relevant CYP450-mediated drug interactions in the ICU. Intensive Care Med 2009 35:603 612.
62. Krishma G, Sansone-Parsons A, Kantesaria B. Drug interaction assessment following concomitant administration of posaconazole and phenytoin in healthy men. Curr Med Res Opin 2007 23:1415 1422.
63. Krishna G, Parsons A, Kantesaria B, Mant T. Evaluation of the pharmacokinetics of posaconazole and rifabutin following co-administration to healthy men. Curr Med Res Opin 2007 23:545 552. (Pubitemid 46456902)
64. Sandiumenge A, Diaz E, Bodi M, Rello J. Therapy of ventilator-associated pneumonia. A patient-based approach based on the ten rules of 'The Tarragona Strategy'. Intensive Care Med 2003 29:876 883.
65. Chamilos G, Lewis RE, Kontoyiannis DP. Delaying amphotericin B-based frontline therapy significantly increases mortality among patients with hematologic malignancy who have zygomycosis. Clin Infect Dis 2008 47:503 509.
66. Trifilio S, Singhal S, Williams S, Frankfurt O, Gordon L, Evens A, Winter J, Tallman M, Pi J, Mehta J. Breakthrough fungal infections after allogeneic hematopoietic stem cell transplantation in patients on prophylactic voriconazole. Bone Marrow Transplant 2007 40:451 456.
67. Mouton JW, Theuretzbacher U, Craig WA, Tulkens PM, Derendorf H, Cars O. Tissue concentrations: do we ever learn? J Antimicrob Chemother 2008 61:235 237.