Intra-Articular Pharmacokinetics of a Gentamicin Impregnated Collagen Sponge in the Canine Stifle: An Experimental Study

Abstract

To investigate local and systemic pharmacokinetics of gentamicin after intra-articular implantation of a gentamicin impregnated collagen sponge (GICS) in the inflamed canine joint. Descriptive repeated measures experimental study. Dogs (n = 9). Stifle joint inflammation was caused by urate injection. Twenty-four hours later a GICS (gentamicin dose, 6 mg/kg) was arthroscopically implanted. Synovial fluid and plasma gentamicin concentrations were measured for 14 days after implantation, and pharmacokinetic parameters modeled using statistical moment analyses. Intra-articular gentamicin concentrations fell to sub-MIC for Staphylococcus sp. (4 µg/mL) by 22.4 hours (95% CI: 18.6-26.2) after sponge implantation. Cmax synovial was 2397 µg/mL (95%CI: 1161-3634 µg/mL) at 1.2 hours (95%CI: 0.5-1.8 hours). Plasma gentamicin concentrations achieved levels of Cmax plasma = 8.0 µg/mL (95%CI: 6.1-10.0 µg/mL) at 1.5 hours (95%CI: 0.8-2.1) after GICS placement and fell below target trough of 2.0 µg/mL by 5.6 hours (95%CI: 4.7-6.5 hours) after GICS placement. Intra-articular gentamicin concentration after GICS placement at an IV-equivalent dose reached high levels and declined rapidly. The maximum plasma levels attained were ∼1/3 of the recommended sub-toxic target for people after parenteral gentamicin administration.