DICLOFENAC

Formulation

The table below describes the formulation of diclofenac sodium and the controls morphine sulfate and gabapentin for the following in vivo experiments.

Experiment(s) Compound Dose(s) mg/kg Correction factor Dose volume mL/kg Route Vehicle Suspension / Solution
Pharmacokinetics Diclofenac 1, 10 1.07 5 PO Water Solution
Irwin, Rotarod Diclofenac 3, 10, 30, 100 1.07 5 PO Water Solution
Plantar incision, Diclofenac 1, 3, 10, 30 1.07 5 PO Water Solution
L5/L6 SNL
Plantar incision, Morphine 6 1.33 1 SC Saline Solution
L5/L6 SNL (Acetone)
L5/L6 SNL (von Frey) Gabapentin 60 1.00 1 PO Saline Solution

L5/L6 SNL = L5/L6 spinal nerve ligation; PO = per os; SC = subcutaneous


Results

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Method: Protein binding
A table shows the results of rapid equilibrium dialysis (RED) and Centrifree centrifugation assays to assess protein binding and stability of diclofenac. In rat plasma in RED, diclofenac was 99.3% bound to protein and 0.7% unbound and had a recovery of 104.2%. In rat brain homogenate in RED, diclofenac was 69.3% bound to protein and 30.7% unbound and had a recovery of 67.6%. In rat plasma in Centrifree, diclofenac was 99.2% bound to protein and 0.8% unbound and had a recovery of 108.2%. In rat brain homogenate in Centrifree, diclofenac was 15.6% bound to protein and 84.4% unbound and had a recovery of 124.9%. Acebutolol, quinidine, and warfarin were included in the study as controls and returned values consistent with literature values in Centrifree assays.

Method: Rotarod Animals were balanced across treatment groups based on body weight. Animals that achieved a latency of 40 seconds during the baseline trial were included in the study. Experimenters assessing behavior were masked to treatment. Group size was determined using power analysis.
Two graphs show the latency for male or female rats to fall off a rotarod apparatus. Responses are shown at the following time points: baseline (before treatment) and at 0.5, 1, and 2 hours after treatment with vehicle (water, delivered PO) or diclofenac (3, 10, 30, or 100 mg/kg, delivered PO). There were 10 rats per group. Significant effects of time and of treatment were found in a two-way repeated measures ANOVA for males, but Dunnett’s tests found no significant pairwise comparisons. Data were analyzed using GraphPad Prism version 10.0.2.


This work was conducted by PsychoGenics Inc. (Paramus, NJ) in collaboration with PSPP, NINDS, NIH under contract # 75N95019D00026. Prescribing information for clinically used controls can be found at labels.fda.gov. Information for icons representing experimental design details can be found through the NINDS Office of Research Quality https://go.nih.gov/Yw2tHGI.