title: Dried blood spot analysis suitable for therapeutic drug monitoring of voriconazole, fluconazole, and posaconazole.
abstract: Invasive aspergillosis and candidemia are important causes of morbidity and mortality in immunocompromised and critically ill patients. The triazoles voriconazole, fluconazole, and posaconazole are widely used for the treatment and prophylaxis of these fungal infections. Due to the variability of the pharmacokinetics of the triazoles among and within individual patients, therapeutic drug monitoring is important for optimizing the efficacy and safety of antifungal treatment. A dried blood spot (DBS) analysis was developed and was clinically validated for voriconazole, fluconazole, and posaconazole in 28 patients. Furthermore, a questionnaire was administered to evaluate the patients' opinions of the sampling method. The DBS analytical method showed linearity over the concentration range measured for all triazoles. Results for accuracy and precision were within accepted ranges; samples were stable at room temperature for at least 12 days; and different hematocrit values and blood spot volumes had no significant influence. The ratio of the drug concentration in DBS samples to that in plasma was 1.0 for voriconazole and fluconazole and 0.9 for posaconazole. Sixty percent of the patients preferred DBS analysis as a sampling method; 15% preferred venous blood sampling; and 25% had no preferred method. There was significantly less perception of pain with the DBS sampling method (P = 0.021). In conclusion, DBS analysis is a reliable alternative to venous blood sampling and can be used for therapeutic drug monitoring of voriconazole, fluconazole, and posaconazole. Patients were satisfied with DBS sampling and had less pain than with venous sampling. Most patients preferred DBS sampling to venous blood sampling.
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Hospital and Clinical Pharmacy, Groningen, the Netherlands.
authors.forename: Kim C M
authors.initials: KC
authors.lastname: van der Elst
authors.forename: Lambert F R
authors.initials: LF
authors.lastname: Span
authors.forename: Kai
authors.initials: K
authors.lastname: van Hateren
authors.forename: Karin M
authors.initials: KM
authors.lastname: Vermeulen
authors.forename: Tjip S
authors.initials: TS
authors.lastname: van der Werf
authors.forename: Ben
authors.initials: B
authors.lastname: Greijdanus
authors.forename: Jos G W
authors.initials: JG
authors.lastname: Kosterink
authors.forename: Donald R A
authors.initials: DR
authors.lastname: Uges
authors.forename: Jan-Willem C
authors.initials: JW
authors.lastname: Alffenaar
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000097:blood* / Q000627:therapeutic use; D001228:Aspergillosis / Q000188:drug therapy; D059788:Dried Blood Spot Testing / Q000379:methods; D016903:Drug Monitoring / Q000379:methods*; D015725:Fluconazole / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D009091:Mucormycosis / Q000188:drug therapy; D009181:Mycoses / Q000188:drug therapy; D014230:Triazoles / Q000097:blood* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole; D015725:Fluconazole
references.citation: Clin Infect Dis. 2009 Mar 1;48(5):503-35
references.pmid: 19191635
references.citation: Mycoses. 2011 Sep;54(5):e301-12
references.pmid: 20557463
references.citation: Clin Infect Dis. 2003 Nov 1;37(9):1172-7
references.pmid: 14557960
references.citation: Clin Infect Dis. 2012 Aug;55(3):381-90
references.pmid: 22610925
references.citation: Ther Drug Monit. 2013 Feb;35(1):133-6
references.pmid: 23188182
references.citation: Clin Infect Dis. 2008 Jan 15;46(2):201-11
references.pmid: 18171251
references.citation: Bioanalysis. 2010 Nov;2(11):1791-6
references.pmid: 21083484
references.citation: Clin Pharmacol Ther. 2010 Jul;88(1):115-9
references.pmid: 20505665
references.citation: Antimicrob Agents Chemother. 2012 Nov;56(11):5758-63
references.pmid: 22926568
references.citation: Pediatr Infect Dis J. 2009 Aug;28(8):717-23
references.pmid: 19593252
references.citation: Antimicrob Agents Chemother. 2011 Oct;55(10):4782-8
references.pmid: 21768513
references.citation: Antimicrob Agents Chemother. 2012 Nov;56(11):5503-10
references.pmid: 22890761
references.citation: Clin Infect Dis. 2004 Jan 15;38(2):161-89
references.pmid: 14699449
references.citation: Antimicrob Agents Chemother. 2005 Aug;49(8):3171-7
references.pmid: 16048920
references.citation: Clin Infect Dis. 2009 May 15;48(10):1441-58
references.pmid: 19361301
references.citation: Curr Pharm Des. 2011;17(27):2931-9
references.pmid: 21834763
references.citation: Antimicrob Agents Chemother. 2012 Jun;56(6):2806-13
references.pmid: 22391534
references.citation: Mycoses. 2011 Nov;54(6):e775-9
references.pmid: 21615538
references.citation: Ther Drug Monit. 2009 Jun;31(3):327-36
references.pmid: 19349929
references.citation: Lancet Infect Dis. 2003 Nov;3(11):685-702
references.pmid: 14592598
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Jan 1;878(1):39-44
references.pmid: 19945360
references.citation: Clin Infect Dis. 2006 Jul 1;43(1):25-31
references.pmid: 16758414
references.citation: Biomed Chromatogr. 2010 Jan;24(1):49-65
references.pmid: 20017122
references.citation: Res Dev Disabil. 1995 Jan-Feb;16(1):51-74
references.pmid: 7701092
references.citation: Transpl Int. 2008 Feb;21(2):140-5
references.pmid: 17944802
references.citation: Antimicrob Agents Chemother. 2013 Feb;57(2):1006-11
references.pmid: 23254425
references.citation: J Antimicrob Chemother. 2012 Nov;67(11):2645-9
references.pmid: 22872447
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2011 May 1;879(15-16):1063-70
references.pmid: 21459055
references.citation: Antimicrob Agents Chemother. 2009 Jan;53(1):24-34
references.pmid: 18955533
references.citation: J Clin Pathol. 1997 Jun;50(6):477-80
references.pmid: 9378812
references.citation: Clin Infect Dis. 2008 Feb 1;46(3):327-60
references.pmid: 18177225
references.citation: Int J Infect Dis. 2009 Jan;13(1):24-36
references.pmid: 18621562
references.citation: Curr Opin Infect Dis. 2008 Dec;21(6):580-6
references.pmid: 18978525
references.citation: Br J Clin Pharmacol. 2009 Feb;67(2):262-3
references.pmid: 19094163
references.citation: J Pharm Biomed Anal. 2011 Jul 15;55(5):1031-40
references.pmid: 21466937
references.citation: Cancer. 1996 Feb 1;77(3):576-86
references.pmid: 8630968
references.citation: Antimicrob Agents Chemother. 2005 Sep;49(9):3640-5
references.pmid: 16127033
references.citation: Ann Rheum Dis. 1978 Aug;37(4):378-81
references.pmid: 686873
references.citation: Antivir Ther. 2013;18(6):821-5
references.pmid: 23234680
references.citation: J Antimicrob Chemother. 2012 May;67(5):1211-6
references.pmid: 22302563
references.citation: Antimicrob Agents Chemother. 2012 Sep;56(9):4793-9
references.pmid: 22751544