Plasma and synovial fluid concentrations of gentamicin in horses after intra-articular administration of buffered and unbuffered gentamicin

SUMMARY The concentration of gentamicin in plasma and synovial fluid of normal adult horses was measured periodically for 24 hours after iv (2.2 mg/kg of body weight), intra-articular (ia; 150 mg), and simultaneous iv and ia administrations. Gentamicin also was buffered with sodium bicarbonate (3 mEq) and then was administered ia and simultaneously iv and ia. Synovial fluid specimens were obtained via an indwelling catheter placed into the antebrachiocarpal joint. The peak mean plasma gentamicin concentration (8.30 μg/ml) after iv administration was significantly (P < 0.05) greater than that (0.69 μg/ml) after ia administration of gentamicin and that (0.55 μg/ml) after administration of gentamicin buffered with sodium bicarbonate. Gentamicin concentration greater than a therapeutic concentration was not attained in the plasma after ia administration of buffered or unbuffered gentamicin. The peak mean synovial fluid concentration (1,828 μg/ml) after ia administration of unbuffered gentamicin was significantly (P < 0.05) greater than that (2.53 μg/ml) after iv administration and significantly (P < 0.05) less than that (5,720 μg/ml) after simultaneous iv and ia administration. The peak mean synovial fluid concentration after ia administration of buffered gentamicin, with and without simultaneous iv administration (2,128 and 2,680 μg/ml, respectively), was not significantly different than that after ia treatment with unbuffered gentamicin. Mean synovial fluid concentration did not differ significantly between groups after ia administration of gentamicin in any combination at postinjection hours 8, 12, and 24, but remained significantly (P < 0.05) greater than that at the same times after iv administration. The mean apparent half-life of gentamicin in the synovial fluid after ia administration (259 minutes) was 2.8 times longer than that in the plasma after iv administration (92 minutes). The mean volume of distribution of gentamicin after iv administration was 297 ml/kg. The mean clearance of gentamicin from the plasma after iv administration was 2.18 ml/min/kg; the mean clearance from the synovial fluid (not normalized for body weight) after ia administration was 1.22 ml/min. Further, the mean synovial fluid concentration of gentamicin remained well above the minimal inhibitory concentration of gentamicin for many common equine bacterial pathogens for 24 hours after ia administration of gentamicin in any combination.