Voriconazole is delivered from antifungal-loaded bone cement.
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.


OBJECTIVE
(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.


CONCLUSIONS
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.
Banner Good Samaritan Medical Center, Banner Orthopaedic Residency, 901 E Willetta Street, 2nd Floor, Phoenix, AZ 85006, USA.
Ryan B
RB
Miller
Alex C
AC
McLaren
Christine
C
Pauken
Henry D
HD
Clarke
Ryan
R
McLemore
D000935:Antifungal Agents / Q000008:administration & dosage*; D001843:Bone Cements / Q000737:chemistry*; D019245:Compressive Strength / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D011743:Pyrimidines / Q000008:administration & dosage*; D014230:Triazoles / Q000008:administration & dosage*; D065819:Voriconazole
D000935:Antifungal Agents; D001843:Bone Cements; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole