The enzymatic basis of drug-drug interactions with systemic triazole antifungals

Clinical Pharmacokinetics

Volumn 47, Issue 12, 2008, Pages 779-792

  Nivoix, Yasmine ^a,c   Levêque, Dominique ^a   Herbrecht, Raoul ^a   Koffel, Jean Claude ^a   Beretz, Laurence ^a   Ubeaud Sequier, Genevieve ^b  

^a UNIVERSITY HOSPITAL OF STRASBOURG   (France)

^b UNIVERSITÉ DE STRASBOURG   (France)

^c HÔPITAL DE HAUTEPIERRE   (France)

Author keywords

Clinical pharmacokinetics; Drug interactions; Fluconazole, drug interactions; Itraconazole, drug interactions; Posaconazole, drug interactions; Triazoles, drug interactions; Voriconazole, drug interactions

Indexed keywords

ABC TRANSPORTER; BREAST CANCER RESISTANCE PROTEIN; CARBAMAZEPINE; CODEINE; CYTOCHROME P450 1A2; CYTOCHROME P450 2C19; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 2E1; CYTOCHROME P450 3A4; DIGOXIN; FLUCONAZOLE; GLYCOPROTEIN P; IMMUNOSUPPRESSIVE AGENT; ITRACONAZOLE; LORAZEPAM; MEVINOLIN; MULTIDRUG RESISTANCE PROTEIN 1; PARACETAMOL; POSACONAZOLE; PREGNANE X RECEPTOR; PROPAFENONE; QUINIDINE; RIFABUTIN; RIFAMPICIN; TRIAZOLE DERIVATIVE; UNINDEXED DRUG; VORICONAZOLE; WARFARIN; ZIDOVUDINE;

ANTIFUNGAL ACTIVITY; BLEEDING; CARDIOTOXICITY; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG DISTRIBUTION; DRUG ELIMINATION; DRUG GLUCURONIDATION; DRUG MECHANISM; DRUG METABOLISM; DRUG MONITORING; ENZYME ACTIVITY; HUMAN; NEUROTOXICITY; PRIORITY JOURNAL; QT PROLONGATION; REVIEW; RHABDOMYOLYSIS; TORSADE DES POINTES;

ANTIFUNGAL AGENTS; CYTOCHROME P-450 ENZYME SYSTEM; DRUG INTERACTIONS; GLUCURONOSYLTRANSFERASE; HUMANS; RECEPTORS, CYTOPLASMIC AND NUCLEAR; TRIAZOLES;

EID: 56749184325     PISSN: 03125963     EISSN: 03125963     Source Type: Journal    
DOI: 10.2165/0003088-200847120-00003     Document Type: Review

References (114)

1. Hoffman HL, Ernst EJ, Klepser ME. Novel triazole antifungal agents. Expert Opin Investig Drugs 2000 Mar; 9 (3): 593-605
2. Koltin Y, Hitchcock CA. The search for new triazole antifungal agents. Curr Opin Chem Biol 1997 Aug; 1 (2): 176-82
3. Sabatelli F, Patel R, Mann PA, et al. 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 Jun; 50 (6): 2009-15
4. Herbrecht R, Nivoix Y, Fohrer C, et al. Management of systemic fungal infections: alternatives to itraconazole. J Antimicrob Chemother 2005 Sep; 56 Suppl. 1: i39-48
5. Kontoyiannis DP, Lionakis MS, Lewis RE, et al. Zygomycosis in a tertiary-care cancer center in the era of Aspergillus-active antifungal therapy: a case-control observational study of 27 recent cases. J Infect Dis 2005 Apr; 191 (8): 1350-60
6. Siwek GT, Dodgson KJ, Magalhaes-Silverman M, et al. Invasive zygomycosis in hematopoietic stem cell transplant recipients receiving voriconazole prophylaxis. Clin Infect Dis 2004 Aug; 39 (4): 584-7
7. Imhof A, Balajee SA, Fredricks DN, et al. Breakthrough fungal infections in stem cell transplant recipients receiving voriconazole. Clin Infect Dis 2004 Sep; 39 (5): 743-6
8. Poirier JM, Cheymol G. Optimisation of itraconazole therapy using target drug concentrations. Clin Pharmacokinet 1998 Dec; 35 (6): 461-73
9. Krieter P, Flannery B, Musick T, et al. Disposition of posaconazole following single-dose oral administration in healthy subjects. Antimicrob Agents Chemother 2004 Sep; 48 (9): 3543-51
10. Roffey SJ, Cole S, Comby P, et al. The disposition of voriconazole in mouse, rat, rabbit, guinea pig, dog, and human. Drug Metab Dispos 2003 Jun; 31 (6): 731-41
11. Debruyne D, Ryckelynck JP. Clinical pharmacokinetics of fluconazole. Clin Pharmacokinet 1993 Jan; 24 (1): 10-27
12. Black DJ, Kunze KL, Wienkers LC, et al. Warfarin-fluconazole: II. A metabolically based drug interaction - in vivo studies. Drug Metab Dispos 1996 Apr; 24 (4): 422-8
13. Kunze KL, Eddy AC, Gibaldi M, et al. Metabolic enantiomeric interactions: the inhibition of human (S)-warfarin-7-hydroxylase by (R)-warfarin. Chirality 1991; 3 (1): 24-9
14. Niwa T, Shiraga T, Takagi A. Effect of antifungal drugs on cytochrome P450 (CYP) 2C9, CYP2C19, and CYP3A4 activities in human liver microsomes. Biol Pharm Bull 2005 Sep; 28 (9): 1805-8
15. Sakaeda T, Iwaki K, Kakumoto M, et al. Effect of micafungin on cytochrome P450 3A4 and multidrug resistance protein 1 activities, and its comparison with azole antifungal drugs. J Pharm Pharmacol 2005 Jun; 57 (6): 759-64
16. Wacher VJ, Wu CY, Benet LZ. Overlapping substrate specificities and tissue distribution of cytochrome P450 3A and P-glycoprotein: implications for drug delivery and activity in cancer chemotherapy. Mol Carcinog 1995 Jul; 13 (3): 129-34
17. Eytan GD, Regev R, Assaraf YG. Functional reconstitution of P-glycoprotein reveals an apparent near stoichiometric drug transport to ATP hydrolysis. J Biol Chem 1996 Feb; 271 (6): 3172-8
18. Ferte J. Analysis of the tangled relationships between P-glycoprotein-mediated multidrug resistance and the lipid phase of the cell membrane. Eur J Biochem 2000 Jan; 267 (2): 277-94
19. Wang EJ, Lew K, Casciano CN, et al. Interaction of common azole antifungals with P glycoprotein. Antimicrob Agents Chemother 2002 Jan; 46 (1): 160-5
20. Gupta A, Unadkat JD, Mao Q. Interactions of azole antifungal agents with the human breast cancer resistance protein (BCRP). J Pharm Sci 2007 Dec; 96 (12): 3226-35
21. Heykants J, Van Peer A, Van de Velde V, et al. The clinical pharmacokinetics of itraconazole: an overview. Mycoses 1989; 32 Suppl.: 167-87
22. Debruyne D. Clinical pharmacokinetics of fluconazole in superficial and systemic mycoses. Clin Pharmacokinet 1997 Jul; 33 (1): 52-77
23. Levêque D, Nivoix Y, Jehl F, et al. Clinical pharmacokinetics of voriconazole. Int J Antimicrob Agents 2006 Apr; 27 (4): 274-84
24. Courtney R, Pai S, Laughlin M, et al. Pharmacokinetics, safety, and tolerability of oral posaconazole administered in single and multiple doses in healthy adults. Antimicrob Agents Chemother 2003 Sep; 47 (9): 2788-95
25. Lazarus HM, Blumer JL, Yanovich S, et al. Safety and pharmacokinetics of oral voriconazole in patients at risk of fungal infection: a dose escalation study. J Clin Pharmacol 2002 Apr; 42 (4): 395-402
26. Schafer-Korting M. Pharmacokinetic optimisation of oral antifungal therapy. Clin Pharmacokinet 1993 Oct; 25 (4): 329-41
27. Slain D, Rogers PD, Cleary JD, et al. Intravenous itraconazole. Ann Pharmacother 2001 Jun; 35 (6): 720-9
28. Van de Velde VJ, Van Peer AP, Heykants JJ, et al. Effect of food on the pharmacokinetics of a new hydroxypropyl-beta-cyclodextrin formulation of itraconazole. Pharmacotherapy 1996 May; 16 (3): 424-8
29. Welage LS, Carver PL, Revankar S, et al. Alterations in gastric acidity in patients infected with human immunodeficiency virus. Clin Infect Dis 1995 Dec; 21 (6): 1431-8
30. Smith D, van de Velde V, Woestenborghs R, et al. The pharmacokinetics of oral itraconazole in AIDS patients. J Pharm Pharmacol 1992 Jul; 44 (7): 618-9
31. Johnson MD, Hamilton CD, Drew RH, et al. A randomized comparative study to determine the effect of omeprazole on the peak serum concentration of itraconazole oral solution. J Antimicrob Chemother 2003 Feb; 51 (2): 453-7
32. Purkins L, Wood N, Ghahramani P, et al. Pharmacokinetics and safety of voriconazole following intravenous- to oral-dose escalation regimens. Antimicrob Agents Chemother 2002 Aug; 46 (8): 2546-53
33. Purkins L, Wood N, Kleinermans D, et al. Effect of food on the pharmacokinetics of multiple-dose oral voriconazole. Br J Clin Pharmacol 2003 Dec; 56 Suppl.: 117-23
34. Purkins L, Wood N, Kleinermans D, et al. Histamine H2-receptor antagonists have no clinically significant effect on the steady-state pharmacokinetics of voriconazole. Br J Clin Pharmacol 2003 Dec; 56 Suppl.: 151-5
35. Courtney R, Wexler D, Radwanski E, et al. Effect of food on the relative bioavailability of two oral formulations of posaconazole in healthy adults. Br J Clin Pharmacol 2004 Feb; 57 (2): 218-22
36. Courtney R, Radwanski E, Lim J, et al. Pharmacokinetics of posaconazole coadministered with antacid in fasting or nonfasting healthy men. Antimicrob Agents Chemother 2004 Mar; 48 (3): 804-8
37. Pearson MM, Rogers PD, Cleary JD, et al. Voriconazole: a new triazole antifungal agent. Ann Pharmacother 2003 Mar; 37 (3): 420-32
38. Schwartz S, Thiel E. CNS-aspergillosis: are there new treatment options? Mycoses 2003; 46 Suppl.: 28-14
39. Black KE, Baden LR. Fungal infections of the CNS: treatment strategies for the immunocompromised patient. CNS Drugs 2007; 21 (4): 293-318
40. Hulsewede JW, Dermoumi H, Ansorg R. Determination of itraconazole and hydroxy-itraconazole in sera using high-performance-liquid-chromatography and a bioassay. Zentralbl Bakteriol 1995 Oct; 282 (4): 457-64
41. Templeton IE, Thummel KE, Kharasch ED, et al. Contribution of itraconazole metabolites to inhibition of CYP3A4 in vivo. Clin Pharmacol Ther 2008 Jan; 83 (1): 77-85
42. Barone JA, Koh JG, Bierman RH, et al. Food interaction and steady-state pharmacokinetics of itraconazole capsules in healthy male volunteers. Antimicrob Agents Chemother 1993 Apr; 37 (4): 778-84
43. Isoherranen N, Kunze KL, Allen KE, et al. Role of itraconazole metabolites in CYP3A4 inhibition. Drug Metab Dispos 2004 Oct; 32 (10): 1121-31
44. 14C]fluconazole in humans. Drug Metab Dispos 1991 Jul; 19 (4): 764-7
45. Hyland R, Jones BC, Smith DA. Identification of the cytochrome P450 enzymes involved in the N-oxidation of voriconazole. Drug Metab Dispos 2003 May; 31 (5): 540-7
46. Ikeda Y, Umemura K, Kondo K, et al. Pharmacokinetics of voriconazole and cytochrome P450 2C19 genetic status. Clin Pharmacol Ther 2004 Jun; 75 (6): 587-8
47. Wexler D, Courtney R, Richards W, et al. Effect of posaconazole on cytochrome P450 enzymes: a randomized, open-label, two-way crossover study. Eur J Pharm Sci 2004 Apr; 21 (5): 645-53
48. US FDA Center for Drug Evaluation and Research. Drug development and drug interactions [online]. Available from URL: http://www.fda.gov/cder/drug/ fluconadrugInteractions/default.htm [Accessed 2008 Oct 12]
49. Banerjee R, Leaver N, Lyster H, et al. Coadministration of itraconazole and tacrolimus after thoracic organ transplantation. Transplant Proc 2001 Feb; 33 (1-2): 1600-2
50. Kwan JT, Foxall PJ, Davidson DG, et al. Interaction of cyclosporin and itraconazole. Lancet 1987 Aug; 2 (8553): 282
51. Ducharme MP, Slaughter RL, Warbasse LH, et al. Itraconazole and hydroxyitraconazole serum concentrations are reduced more than tenfold by phenytoin. Clin Pharmacol Ther 1995 Dec; 58 (6): 617-24
52. Ahonen J, Olkkola KT, Neuvonen PJ. Effect of route of administration of fluconazole on the interaction between fluconazole and midazolam. Eur J Clin Pharmacol 1997; 51 (5): 415-9
53. Olkkola KT, Ahonen J, Neuvonen PJ. The effects of the systemic antimycotics, itraconazole and fluconazole, on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam. Anesth Analg 1996 Mar; 82 (3): 511-6
54. Gubbins PO, McConnell SA, Amsden JR. Antifungal agents. In: Piscitelli SC, Rodvold KA, editors. Drug interactions in infectious diseases. 2nd ed. Totowa (NJ): Humana Press, 2005: 289-337
55. Kiang TK, Ensom MH, Chang TK. UDP-glucuronosyltransferases and clinical drug-drug interactions. Pharmacol Ther 2005 Apr; 106 (1): 97-132
56. Sahai J, Gallicano K, Pakuts A, et al. Effect of fluconazole on zidovudine pharmacokinetics in patients infected with human immunodeficiency virus. J Infect Dis 1994 May; 169 (5): 1103-7
57. Ghosal A, Hapangama N, Yuan Y, et al. Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of posaconazole (Noxafil). Drug Metab Dispos 2004 Feb; 32 (2): 267-71
58. Krishna G, Sansone-Parsons A, Kantesaria B. Drug interaction assessment following concomitant administration of posaconazole and phenytoin in healthy men. Curr Med Res Opin 2007 Jun; 23 (6): 1415-22
59. Gubbins PO. Mould-active azoles: pharmacokinetics, drug interactions in neutropenic patients. Curr Opin Infect Dis 2007 Dec; 20 (6): 579-86
60. Ho RH, Kim RB. Transporters and drug therapy: implications for drug disposition and disease. Clin Pharmacol Ther 2005 Sep; 78 (3): 260-77
61. Purkins L, Wood N, Kleinermans D, et al. Voriconazole does not affect the steady-state pharmacokinetics of digoxin. Br J Clin Pharmacol 2003 Dec; 56 Suppl.: 145-50
62. de Lannoy IA, Silverman M. The MDR1 gene product, P-glycoprotein, mediates the transport of the cardiac glycoside, digoxin. Biochem Biophys Res Commun 1992 Nov; 189 (1): 551-7
63. Xia CQ, Yang JJ, Gan LS. Breast cancer resistance protein in pharmacokinetics and drug-drug interactions. Expert Opin Drug Metab Toxicol 2005 Dec; 1 (4): 595-611
64. Willson TM, Kliewer SA. PXR, CAR and drug metabolism. Nat Rev Drug Discov 2002 Apr; 1 (4): 259-66
65. Duret C, Daujat-Chavanieu M, Pascussi JM, et al. Ketoconazole and miconazole are antagonists of the human glucocorticoid receptor: consequences on the expression and function of the constitutive androstane receptor and the pregnane X receptor. Mol Pharmacol 2006 Jul; 70 (1): 329-39
66. Ghahramani P, Purkins L, Kleinermans D, et al. Effects of rifampicin and rifabutin on the pharmacokinetics of voriconazole [abstract no. 844]. 40th Annual Meeting of the Infectious Diseases Society of America; 2000 Sep 24-27; Toronto (ON)
67. Baciewicz AM, Menke JJ, Bokar JA, et al. Fluconazole-warfarin interaction. Ann Pharmacother 1994 Sep; 28 (9): 1111
68. Crussell-Porter LL, Rindone JP, Ford MA, et al. Low-dose fluconazole therapy potentiates the hypoprothrombinemic response of warfarin sodium. Arch Intern Med 1993 Jan; 153 (1): 102-4
69. Gericke KR. Possible interaction between warfarin and fluconazole. Pharmacotherapy 1993 Sep; 13 (5): 508-9
70. Kunze KL, Trager WF. Warfarin-fluconazole: III. A rational approach to management of a metabolically based drug interaction. Drug Metab Dispos 1996 Apr; 24 (4): 429-35
71. Kunze KL, Wienkers LC, Thummel KE, et al. Warfarin-fluconazole: I. Inhibition of the human cytochrome P450-dependent metabolism of warfarin by fluconazole - in vitro studies. Drug Metab Dispos 1996 Apr; 24 (4): 414-21
72. Allison Jr EJ, McKinney TJ, Langenberg JN. Spinal epidural haematoma as a result of warfarin/fluconazole drug interaction. Eur J Emerg Med 2002 Jun; 9 (2): 175-7
73. Mootha VV, Schluter ML, Das A. Intraocular hemorrhages due to warfarin fluconazole drug interaction in a patient with presumed Candida endophthalmitis. Arch Ophthalmol 2002 Jan; 120 (1): 94-5
74. Purkins L, Wood N, Kleinermans D, et al. Voriconazole potentiates warfarin-induced prothrombin time prolongation. Br J Clin Pharmacol 2003 Dec; 56 Suppl.: 124-9
75. Neuvonen PJ, Jalava KM. Itraconazole drastically increases plasma concentrations of lovastatin and lovastatin acid. Clin Pharmacol Ther 1996 Jul; 60 (1): 54-61
76. Damkier P, Hansen LL, Brosen K. Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine. Br J Clin Pharmacol 1999 Dec; 48 (6): 829-38
77. Kaukonen KM, Olkkola KT, Neuvonen PJ. Itraconazole increases plasma concentratrations of quinidine. Clin Pharmacol Ther 1997 Nov; 62 (5): 510-7
78. Alderman CP, Jersmann HP. Digoxin-itraconazole interaction. Med J Aust 1993 Dec; 159 (11-12): 838-9
79. Angirasa AK, Koch AZ. P-glycoprotein as the mediator of itraconazole-digoxin interaction. J Am Podiatr Med Assoc 2002 Sep; 92 (8): 471-2
80. Jalava KM, Partanen J, Neuvonen PJ. Itraconazole decreases renal clearance of digoxin. Ther Drug Monit 1997 Dec; 19 (6): 609-13
81. Brockmeyer NH, Tillmann I, Mertins L, et al. Pharmacokinetic interaction of fluconazole and zidovudine in HIV-positive patients. Eur J Med Res 1997 Sep; 2 (9): 377-83
82. Krishna G, Parsons A, Kantesaria B, et al. Evaluation of the pharmacokinetics of posaconazole and rifabutin following co-administration to healthy men. Curr Med Res Opin 2007 Mar; 23 (3): 545-52
83. Purkins L, Wood N, Ghahramani P, et al. Coadministration of voriconazole and phenytoin: pharmacokinetic interaction, safety, and toleration. Br J Clin Pharmacol 2003 Dec; 56 Suppl.: 137-44
84. Blum RA, Wilton JH, Hilligoss DM, et al. Effect of fluconazole on the disposition of phenytoin. Clin Pharmacol Ther 1991 Apr; 49 (4): 420-5
85. Bonay M, Jonville-Bera AP, Diot P, et al. Possible interaction between phenobarbital, carbamazepine and itraconazole. Drug Saf 1993; 9 (4): 309-11
86. Vfend® IV (voriconazone) for injection [US prescribing information; online]. Available from URL: http://www.pfizer.com/files/products/uspi_vfend.pdf [Accessed 2008 Oct 12]
87. Yeh J, Soo SC, Summerton C, et al. Potentiation of action of warfarin by itraconazole. BMJ 1990 Sep; 301 (6753): 669
88. Saad AH, DePestel DD, Carver PL. Factors influencing the magnitude and clinical significance of drug interactions between azole antifungals and select immunosuppressants. Pharmacotherapy 2006 Dec; 26 (12): 1730-44
89. Wang RW, Kari PH, Lu AY, et al. Biotransformation of lovastatin: IV. Identification of cytochrome P450 3A proteins as the major enzymes responsible for the oxidative metabolism of lovastatin in rat and human liver microsomes. Arch Biochem Biophys 1991 Nov; 290 (2): 355-61
90. Hirano M, Maeda K, Matsushima S, et al. Involvement of BCRP (ABCG2) in the biliary excretion of pitavastatin. Mol Pharmacol 2005 Sep; 68 (3): 800-7
91. Cooper KJ, Martin PD, Dane AL, et al. Effect of itraconazole on the pharmacokinetics of rosuvastatin. Clin Pharmacol Ther 2003 Apr; 73 (4): 322-9
92. Liu P, Foster G, LaBadie RR, et al. Pharmacokinetic interaction between voriconazole and efavirenz at steady state in healthy male subjects. J Clin Pharmacol 2008 Jan; 48 (1): 73-84
93. Ishigam M, Uchiyama M, Kondo T, et al. Inhibition of in vitro metabolism of simvastatin by itraconazole in humans and prediction of in vivo drug-drug interactions. Pharm Res 2001 May; 18 (5): 622-31
94. Ishigami M, Kawabata K, Takasaki W, et al. Drug interaction between simvastatin and itraconazole in male and female rats. Drug Metab Dispos 2001 Jul; 29 (7): 1068-72
95. Kantola T, Kivisto KT, Neuvonen PJ. Effect of itraconazole on the pharmacokinetics of atorvastatin. Clin Pharmacol Ther 1998 Jul; 64 (1): 58-65
96. Kantola T, Kivisto KT, Neuvonen PJ. Effect of itraconazole on cerivastatin pharmacokinetics. Eur J Clin Pharmacol 1999 Jan; 54 (11): 851-5
97. Kivisto KT, Kantola T, Neuvonen PJ. Different effects of itraconazole on the pharmacokinetics of fluvastatin and lovastatin. Br J Clin Pharmacol 1998 Jul; 46 (1): 49-53
98. Mazzu AL, Lasseter KC, Shamblen EC, et al. Itraconazole alters the pharmacokinetics of atorvastatin to a greater extent than either cerivastatin or pravastatin. Clin Pharmacol Ther 2000 Oct; 68 (4): 391-400
99. Neuvonen PJ, Kantola T, Kivisto KT. Simvastatin but not pravastatin is very susceptible to interaction with the CYP3A4 inhibitor itraconazole. Clin Pharmacol Ther 1998 Mar; 63 (3): 332-41
100. Backman JT, Kivisto KT, Olkkola KT, et al. The area under the plasma concentration-time curve for oral midazolam is 400-fold larger during treatment with itraconazole than with rifampicin. Eur J Clin Pharmacol 1998 Mar; 54 (1): 53-8
101. Olkkola KT, Backman JT, Neuvonen PJ. Midazolam should be avoided in patients receiving the systemic antimycotics ketoconazole or itraconazole. Clin Pharmacol Ther 1994 May; 55 (5): 481-5
102. Ahonen J, Olkkola KT, Neuvonen PJ. Effect of itraconazole and terbinafine on the pharmacokinetics and pharmacodynamics of midazolam in healthy volunteers. Br J Clin Pharmacol 1995 Sep; 40 (3): 270-2
103. Neuvonen PJ, Varhe A, Olkkola KT. The effect of ingestion time interval on the interaction between itraconazole and triazolam. Clin Pharmacol Ther 1996 Sep; 60 (3): 326-31
104. Varhe A, Olkkola KT, Neuvonen PJ. Oral triazolam is potentially hazardous to patients receiving systemic antimycotics ketoconazole or itraconazole. Clin Pharmacol Ther 1994 Dec; 56 (6 Pt 1): 601-7
105. Liu P, Foster G, Gandelman K, et al. Steady-state pharmacokinetic and safety profiles of voriconazole and ritonavir in healthy male subjects. Antimicrob Agents Chemother 2007 Oct; 51 (10): 3617-26
106. Chan JD. Pharmacokinetic drug interactions of vinca alkaloids: summary of case reports. Pharmacotherapy 1998 Nov; 18 (6): 1304-7
107. Gillies J, Hung KA, Fitzsimons E, et al. Severe vincristine toxicity in combination with itraconazole. Clin Lab Haematol 1998 Apr; 20 (2): 123-4
108. Sadaba B, Campanero MA, Quetglas EG, et al. Clinical relevance of sirolimus drug interactions in transplant patients. Transplant Proc 2004 Dec; 36 (10): 3226-8
109. Mathis AS, Shah NK, Friedman GS. Combined use of sirolimus and voriconazole in renal transplantation: a report of two cases. Transplant Proc 2004 Nov; 36 (9): 2708-9
110. Marty FM, Lowry CM, Cutler CS, et al. Voriconazole and sirolimus coadministration after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2006 May; 12 (5): 552-9
111. Glasmacher A, Prentice A, Gorschluter M, et al. Itraconazole prevents invasive fungal infections in neutropenic patients treated for hematologic malignancies: evidence from a meta-analysis of 3,597 patients. J Clin Oncol 2003 Dec; 21 (24): 4615-26
112. Pascual A, Calandra T, Bolay S, et al. Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes. Clin Infect Dis 2008 Jan; 46 (2): 201-11
113. Trifilio S, Pennick G, Pi J, et al. Monitoring plasma voriconazole levels may be necessary to avoid subtherapeutic levels in hematopoietic stem cell transplant recipients. Cancer 2007 Apr; 109 (8): 1532-5
114. Walsh TJ, Raad I, Patterson TF, et al. 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 Jan; 44 (1): 2-12