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.
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.
Authors: Alex C McLaren; Matt Nugent; Kostas Economopoulos; Himanshu Kaul; Brent L Vernon; Ryan McLemore Journal: Clin Orthop Relat Res Date: 2009-04-24 Impact factor: 4.176
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