Abstract
Background
Local delivery of antifungals is an important modality in managing orthopaedic fungal infection. Voriconazole is a powder antifungal suitable for addition to bone cement that is released from bone cement but the mechanical properties of antimicrobial-loaded bone cement (ALBC) made with voriconazole are unknown.
Questions/Purposes
(1) Is voriconazole release dose-dependent? (2) Is released voriconazole active? (3) Is the loss of ALBC’s compressive strength caused by voriconazole dose- and elution-dependent?
Methods
Sixty standard test cylinders were fabricated with ALBC: 300 or 600 mg voriconazole per batch eluted for 30 days in deionized water. Voriconizole concentration in the eluate was measured using high-performance liquid chromatography. Cumulative-released voriconizole was calculated. Biologic activity was tested. Compressive strength was measured before and after elution. The effect of dose and time on release and compressive strength were analyzed using repeated-measure analysis of variance.
Results
Fifty-seven percent and 63% of the loaded voriconazole were released by Day 30 for the 300-mg and 600-mg formulations, respectively. The released voriconazole was active on bioassay. Compressive strength was reduced from 79 MPa to 53 MPa and 69 MPa to 31 MPa by 30 days for the 300-mg and 600-mg formulations, respectively.
Conclusions
Voriconazole release from ALBC increases with dose and is bioactive. Loss in compressive strength is greater after elution and with higher dose.
Clinical Relevance
Three hundred milligrams of voriconazole in ALBC would be expected to deliver meaningful amounts of active drug in vivo. The compressive strength of ALBC with 600 mg voriconazole is less than expected compared to commonly used antibacterials.
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Acknowledgments
We acknowledge the help of Mary Martin PharmD at Banner Good Samaritan Medical Center and Francis Calara, BSE, at ASU. We further acknowledge assistance from John Lopez and Zachary Laughrey from the ASU Proteomics Laboratory.
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One or more of the authors received funding from the Herbert Louis Fund at the OREF (ACM) and the donation of voriconazole by Banner Good Samaritan Medical Center (RBM). Banner Good Samaritan Medical Center provided financial support for one of the authors (RM).
All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research editors and board members are on file with the publication and can be viewed on request.
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Miller, R.B., McLaren, A.C., Pauken, C. et al. Voriconazole Is Delivered From Antifungal-Loaded Bone Cement. Clin Orthop Relat Res 471, 195–200 (2013). https://doi.org/10.1007/s11999-012-2463-8
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DOI: https://doi.org/10.1007/s11999-012-2463-8