Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jul 30;14(8):1598.
doi: 10.3390/pharmaceutics14081598.

Therapeutic Drug Monitoring of Sputum Voriconazole in Pulmonary Aspergillosis

Affiliations

Therapeutic Drug Monitoring of Sputum Voriconazole in Pulmonary Aspergillosis

Sacha Sarfati et al. Pharmaceutics. .

Abstract

Voriconazole is one of the most used antifungal azoles against pulmonary aspergillosis. Therapeutic drug monitoring (TDM) of the voriconazole concentration in plasma is recommended in clinical practice guidelines to prevent treatment failure and toxicity. The aim of this study was to evaluate the feasibility and utility of TDM of the voriconazole concentration in the sputum of patients treated for pulmonary aspergillosis. Fifty sputum and 31 plasma samples were analysed with high-performance tandem mass spectrometry (HPLC-MS/MS) in 24 patients included in the study. The voriconazole concentration was simultaneously assessed in the plasma and sputum in 22 samples. The correlation between the sputum and plasma levels was estimated with a univariate linear regression model, and the observed R2 was 0.86. We determined the following equation, Csputum = 0.45 (Cplasma) + 0.21, which could predict the voriconazole concentration in plasma from sputum. TDM of the voriconazole concentration in sputum is an easy, non-invasive and accurate method with which to evaluate voriconazole exposure in patients with pulmonary aspergillosis.

Keywords: pulmonary aspergillosis; sputum; therapeutic drug monitoring; trough concentration; voriconazole.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Percentage of voriconazole diffusion rate between sputum and plasma.
Figure 2
Figure 2
Correlation between plasma and sputum voriconazole concentrations.
Figure 3
Figure 3
Concentration of voriconazole in sputum over time after dose administration for five patients.
Figure 4
Figure 4
Percentage of samples with Cmin > MIC in sputum and plasma. MIC = minimum inhibitory concentration.

References

    1. Ullmann A.J., Aguado J.M., Arikan-Akdagli S., Denning D.W., Groll A.H., Lagrou K., Lass-Flörl C., Lewis R.E., Munoz P., Verweij P.E., et al. Diagnosis and management of Aspergillus diseases: Executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin. Microbiol. Infect. 2018;24((Suppl. 1)):e1–e38. doi: 10.1016/j.cmi.2018.01.002. - DOI - PubMed
    1. Denning D.W., Cadranel J., Beigelman-Aubry C., Ader F., Chakrabarti A., Blot S., Ullmann A.J., Dimopoulos G., Lange C. European Society for Clinical Microbiology and Infectious Diseases and European Respiratory Society. Chronic pulmonary aspergillosis: Rationale and clinical guidelines for diagnosis and management. Eur. Respir. J. 2016;47:45–68. doi: 10.1183/13993003.00583-2015. - DOI - PubMed
    1. Pascual A., Calandra T., Bolay S., Buclin T., Bille J., Marchetti O. Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes. Clin. Infect. Dis. 2008;46:201–211. doi: 10.1086/524669. - DOI - PubMed
    1. Kim S.H., Yim D.S., Choi S.M., Kwon J.C., Han S., Lee D.G., Park C., Kwon E.Y., Park S.H., Choi J.H., et al. Voriconazole-related severe adverse events: Clinical application of therapeutic drug monitoring in Korean patients. Int. J. Infect. Dis. 2011;15:e753–e758. doi: 10.1016/j.ijid.2011.06.004. - DOI - PubMed
    1. Gautier-Veyret E., Truffot A., Bailly S., Fonrose X., Thiebaut-Bertrand A., Tonini J., Cahn J.Y., Stanke-Labesque F. Inflammation is a potential risk factor of voriconazole overdose in hematological patients. Fundam. Clin. Pharmacol. 2019;33:232–238. doi: 10.1111/fcp.12422. - DOI - PubMed

LinkOut - more resources