The main pharmacodynamic parameters (potency, efficacy, and sensitivity) were estimated for four endpoints (body temperature, creeping speed, ground vertical reaction force and clinical lameness score).
Creeping time was measured (in seconds) in a tunnel 6.38 m long, using a stopwatch (digital stopwatch) in triplicate for each time point and creeping speed (m/s) was used as the final measurement for this endpoint.
For rectal temperature, creeping speed, overall clinical lameness score and ground reaction vertical force, a nearly maximal effect of cimicoxib was predicted to occur for doses of 1, 1.5, 2, and 3 mg/kg, respectively.
The overall maximal effects for the two groups of dogs were 86% for the body temperature, 66% for the ground reaction vertical force and 76% for the creeping speed.
Thus, the anti-inflammatory effect of cimicoxib consisted in a reduction of pain (decrease of Kout) and the same model as for the creeping speed under the tunnel was used (see Equation 5).
For the body temperature, the paw circumference, the creeping speed, the vertical normalised force obtained with a force plate and the analgesic effect, the maximal estimated effect was expressed as a percentage of control value, a 100% maximum effect indicating a return to control value (no kaolin challenge).
The plasma concentration corresponding to half the maximum of the indirect effect were 239 μg/L for creeping speed, 284 μg/L for the lameness score, 161 μg/L for the ground reaction vertical force and 193 μg/L for the body temperature.
Finally, four endpoints were considered as suitable for the PK/PD analysis aiming at modelling the relationship between cimicoxib plasma concentrations and its antipyretic and anti-inflammatory effects, namely: body temperature (antipyretic effect), creeping speed, vertical force of the paw and clinical lameness score (anti-inflammatory effects).
THE CREEP sped to the early lead and angled in, dueled inside, fought back along the rail in the stretch and weakened some late.
If you have cruise control in your vehicle, use it regularly so that you don't subconsciously "creep" your speed upwards.
There's even an optional button on the dash to lift the front axle 1.18 inches for creeping over speed bumps.
