A DUAL ANTIBIOTIC (GENTAMICIN/CLINDAMYCIN) SUSTAINED-RELEASE INJECTABLE FORMULATION (CC-G/C) OFFERS HIGH AND SUSTAINED CONCENTRATIONS OF GENTAMICIN AND CLINDAMYCIN IN BONE FOLLOWING INTRAOSSEUS INJECTION

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Aim The novel carbohydrate-ester based antibiotic-eluting depot technology CC-G/C has shown great promise in terms of efficacy in an osteomyelitis pig model. The present study aimed to investigate the initial release kinetics of gentamicin and clindamycin from CC-G/C in trabecular bone after a thin needle intraosseous injection. Method In the tibial metaphysis of 4 pigs (both hindlegs, n=8), microdialysis catheters were placed 5 and 10 mm from an intraosseous injected CC-G/C depot. 1.5 mL of the carbohydrate-ester based CC-G/C was injected using a 21G needle. Sampling was performed for 12 consecutive hours, to evaluate gentamicin and clindamycin concentrations in trabecular bone and subcutaneous tissue adjacent to the knee joint. Plasma samples were taken to determine systemic spillover. Results Across trabecular bone locations, a mean peak-drug concentration range of 471-524 µg/mL was observed for gentamicin and 681-788 µg/mL for clindamycin. The mean concentration range at 12 hours was 126-321 µg/mL for gentamicin and 255-594 µg/mL for clindamycin. Low concentrations of both drugs were found in subcutaneous tissue adjacent to the knee joint (< 1 µg/mL) and plasma (< 0.2 µg/mL). Conclusions The carbohydrate-ester based drug delivery technology CC-G/C provides high and sustained local concentrations of gentamicin and clindamycin for at least 12 hours after intraosseous injection with negligible systemic spillover. The data bolsters the potential benefit of improved local antibiotic delivery systems with flexible administration in target tissues for future therapeutic strategies addressing orthopaedic infections.

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