To compare the degree of white line separation created by increasing physiologic loads between bovine claws with and without toe-tip necrosis (TTN).
Cadaveric bovine hind limbs with (n = 10) and without (10) TTN.
Hind limbs in which 1 or both claws had evidence of apical white line separation were considered to have TTN. Hind limbs in which neither claw had evidence of white line separation were considered controls. Each hind limb was mounted in a materials testing system with the bottom surface of the hoof angled at approximately 5° to the horizontal plane such that the apex of the claws made initial contact with the clear testing surface to simulate physiologic loading conditions. A digital camera mounted underneath the testing surface was used to obtain images of the bottom of the hoof during the application of each of 3 increasing static loads (1, 2, and 3 kN). The images were analyzed with commercial image-processing software to quantify white line separation area.
White line separation area was significantly greater for claws with TTN than for control claws and increased as the applied load increased. White line separation was almost nonexistent in control claws and was not affected by increasing load.
CONCLUSIONS AND CLINICAL RELEVANCE
Results suggested that mechanical loading exacerbated TTN, but compressive loading alone, even at excessive levels, did not initiate the condition. Interventions (eg, hoof blocks) that decrease loading of affected claws may be beneficial for the treatment of TTN at its earliest stages.
Objective—To determine pharmacokinetics and plasma steady-state kinetics of metformin after oral or nasogastric administration in insulin-resistant (IR) ponies
Animals—8 IR ponies
Procedures—Metformin (30 mg/kg) was administered to 8 ponies via nasogastric tube Blood samples were collected at intervals for 24 hours. Plasma concentrations of metformin were measured via liquid chromatography-electrospray tandem mass spectroscopy Pharmacokinetic variables were determined via noncompartmental analysis. Metformin (15 mg/kg, PO, twice daily [8 am and 5 pm]) was administered to 4 ponies for an additional 20 days, and blood samples were obtained every 2 days. Plasma concentration at steady state (Css) was determined.
Results—Mean ± SD elimination half-life (t1/2) of metformin was 11.7 ± 5.2 hours, maxima plasma concentration was 748 ± 269 ng/mL at 54 ± 32 minutes, mean area under the curve was 355 ± 92μg•h/mL, and apparent clearance was 90.6 ± 28.1 mL/min/kg. The Css was 122 ± 22 ng/mL.
Conclusions and Clinical Relevance—Metformin reportedly enhances insulin sensitivity of peripheral tissues without stimulating insulin secretion, but bioavailability in horses is low. The t1/2 of metformin in IR ponies was similar to that in humans. Actual clearance of metformin adjusted for bioavailability in IR ponies was similar to that in humans; however, during chronic oral administration at dosages reported in efficacy studies, the Css of metformin was less than values associated with therapeutic efficacy in humans The apparent lack of long-term efficacy of metformin in horses is likely attributable to low bioavailability, rather than to rapid clearance. (Am J Vet Res 2010;71:1201-1206)