PHARMACOKINETICS OF A DEGRADABLE DRUG-DELIVERY SYSTEM IN BONE

Local delivery of antibiotics via a degradable carrier has the potenti al for high local antibiotic levels and avoids systemic toxicity Intra venous access, renal function monitoring, and later surgical removal m ay not be required when degradable local delivery modalities are used. This study examined the in vivo elution of gentamicin from processed bovine collagen (Type I). Gentamicin impregnated collagen (3 mg/kg) wa s implanted into the femoral medullary canal of 45 adult white rabbits . The gentamicin was released into the bone and averaged greater than 600 mu g/ml during the initial 48 hours. Local hone levels fell to 144 .40 +/- 229.84 mu g/ml at 5 days and were subsequently greater than or equal to 10.30 +/- 5.02 mu g/ml through Day 28. Serum levels reached an average peak of 1.25 +/- 0.29 mu g/ml 5 hours after implantation an d fell below 1.0 mu g/ml at 12 hours after implantation. Serum levels subsequently averaged less than or equal to 0.63 +/- 0.09 mu g/ml thro ugh Day 28, Collagen impregnated with gentamicin proved to be an effec tive degradable carrier of gentamicin in the healthy rabbit; it provid ed local bone concentrations above the minimum inhibitory concentratio n of gentamicin and serum concentrations below levels associated with systemic toxicity as long as 28 days after implantation.