title: Bioavailability of voriconazole in hospitalised patients.
abstract: An important element in antimicrobial stewardship programmes is early switch from intravenous (i.v.) to oral antimicrobial treatment, especially for highly bioavailable drugs. The antifungal agent voriconazole is available both in i.v. and oral formulations and bioavailability is estimated to be >90% in healthy volunteers, making this drug a suitable candidate for such a transition. Recently, two studies have shown that the bioavailability of voriconazole is substantially lower in patients. However, for both studies various factors that could influence the voriconazole serum concentration, such as inflammation, concomitant intake of food with oral voriconazole, and gastrointestinal complications, were not included in the evaluation. Therefore, in this study a retrospective chart review was performed in adult patients treated with both oral and i.v. voriconazole at the same dose and within a limited (≤5 days) time interval in order to evaluate the effect of switching the route of administration on voriconazole serum concentrations. A total of 13 patients were included. The mean voriconazole trough concentration was 2.28 mg/L [95% confidence interval (CI) 1.29-3.26 mg/L] for i.v. voriconazole administration and 2.04 mg/L (95% CI 0.78-3.30 mg/L) for oral administration. No significant difference was found in the mean oral and i.v. trough concentrations of voriconazole (P = 0.390). The mean bioavailability was 83.0% (95% CI 59.0-107.0%). These findings suggest that factors other than bioavailability may cause the observed difference in voriconazole trough concentrations between oral and i.v. administration in the earlier studies and stress the need for an antimicrobial stewardship team to guide voriconazole dosing.
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors.forename: Anette
authors.initials: A
authors.lastname: Veringa
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors.forename: Sanne
authors.initials: S
authors.lastname: Geling
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Haematology, Groningen, The Netherlands.
authors.forename: Lambert F R
authors.initials: LF
authors.lastname: Span
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, The Netherlands.
authors.forename: Karin M
authors.initials: KM
authors.lastname: Vermeulen
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Critical Care, Groningen, The Netherlands.
authors.forename: Jan G
authors.initials: JG
authors.lastname: Zijlstra
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Internal Medicine, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases and Tuberculosis, Groningen, The Netherlands.
authors.forename: Tjip S
authors.initials: TS
authors.lastname: van der Werf
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; University of Groningen, Department of Pharmacy, Section of Pharmacotherapy and Pharmaceutical Care, Groningen, The Netherlands.
authors.forename: Jos G W
authors.initials: JG
authors.lastname: Kosterink
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. Electronic address: j.w.c.alffenaar@umcg.nl.
authors.forename: Jan-Willem C
authors.initials: JC
authors.lastname: Alffenaar
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001682:Biological Availability; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D044967:Serum / Q000737:chemistry; D013997:Time Factors; D065819:Voriconazole / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D065819:Voriconazole
keywords: Antifungal stewardship; Bioavailability; Pharmacokinetics; Therapeutic drug monitoring; Voriconazole