title: Monitoring trough voriconazole plasma concentrations in haematological patients: real life multicentre experience.
abstract: The objective of this retrospective study was to evaluate results from voriconazole therapeutic drug monitoring (TDM) in haematological patients in routine clinical practice. Between 2005 and 2010, 1228 blood samples were obtained from 264 haematological patients (median 3 samples/patient; range 1-27) receiving voriconazole for targeted/preemptive treatment of invasive aspergillosis (IA) (46.3% of samples), empirical therapy (12.9%) or prophylaxis (40.8%). A high-pressure liquid chromatography assay was used to analyse voriconazole concentrations. Clinical and laboratory data were analysed retrospectively. The median of the detected voriconazole plasma concentration was 1.00 μg ml(-1) (range <0.20-13.47 μg ml(-1)). Significant inter- and intra-patients variability of measured concentrations (81.9% and 50.5%) were identified. With the exception of omeprazole administration, there was no relevant relationship between measured voriconazole concentrations and drug dose, route administration, age, gender, CYP2C19*2 genotype, gastrointestinal tract abnormality, administration via nasogastric tube, serum creatinine, and liver enzymes. However, per patient analysis identified significant role of individual voriconazole dose and drug form change on measured plasma concentration. Measured voriconazole concentrations did not correlate with the treatment outcome of patients with IA. We only identified a limited number of adverse events related to voriconazole therapy; however, the median plasma concentration was not different from concentrations measured in samples without reported toxicity. Our retrospective study has suggested that routine monitoring of voriconazole plasma concentrations has probably only a limited role in daily haematological practice.
authors.affiliation: Department of Internal Medicine-Hematology and Oncology, University Hospital Brno, Masaryk University, Brno, Czech Republic. zracil@fnbrno.cz
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Racil
authors.forename: Jana
authors.initials: J
authors.lastname: Winterova
authors.forename: Michal
authors.initials: M
authors.lastname: Kouba
authors.forename: Pavel
authors.initials: P
authors.lastname: Zak
authors.forename: Ludmila
authors.initials: L
authors.lastname: Malaskova
authors.forename: Lucie
authors.initials: L
authors.lastname: Buresova
authors.forename: Martina
authors.initials: M
authors.lastname: Toskova
authors.forename: Martina
authors.initials: M
authors.lastname: Lengerova
authors.forename: Iva
authors.initials: I
authors.lastname: Kocmanova
authors.forename: Barbora
authors.initials: B
authors.lastname: Weinbergerova
authors.forename: Shira
authors.initials: S
authors.lastname: Timilsina
authors.forename: Monika
authors.initials: M
authors.lastname: Rolencova
authors.forename: Petr
authors.initials: P
authors.lastname: Cetkovsky
authors.forename: Jiri
authors.initials: J
authors.lastname: Mayer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001228:Aspergillosis / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005260:Female; D006402:Hematologic Diseases / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood*; D012189:Retrospective Studies; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood*; D065819:Voriconazole; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D065819:Voriconazole