title: Pharmacokinetics of a degradable drug delivery system in bone.
abstract: Local delivery of antibiotics via a degradable carrier has the potential for high local antibiotic levels and avoids systemic toxicity. Intravenous access, renal function monitoring, and later surgical removal may 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) was implanted into the femoral medullary canal of 45 adult white rabbits. The gentamicin was released into the bone and averaged greater than 600 micrograms/ml during the initial 48 hours. Local bone levels fell to 144.40 +/- 229.84 micrograms/ml at 5 days and were subsequently greater than or equal to 10.30 +/- 5.02 micrograms/ml through Day 28. Serum levels reached an average peak of 1.25 +/- 0.29 micrograms/ml 5 hours after implantation and fell below 1.0 microgram/ml at 12 hours after implantation. Serum levels subsequently averaged less than or equal to 0.63 +/- 0.09 microgram/ml through Day 28. Collagen impregnated with gentamicin proved to be an effective degradable carrier of gentamicin in the healthy rabbit; it provided local bone concentrations above the minimum inhibitory concentration of gentamicin and serum concentrations below levels associated with systemic toxicity as long as 28 days after implantation.
authors.affiliation: Division of Orthopaedic Surgery, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Humphrey
authors.forename: S
authors.initials: S
authors.lastname: Mehta
authors.forename: A V
authors.initials: AV
authors.lastname: Seaber
authors.forename: T P
authors.initials: TP
authors.lastname: Vail
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000032:analysis / Q000493:pharmacokinetics*; D001842:Bone and Bones / Q000378:metabolism*; D003094:Collagen; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005839:Gentamicins / Q000032:analysis / Q000493:pharmacokinetics*; D008826:Microbial Sensitivity Tests; D019736:Prostheses and Implants; D011817:Rabbits
chemical_list: D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D005839:Gentamicins; D003094:Collagen