INJECTION SITE REACTION TO REPEATED INTRAVENOUS BOLUS INJECTION OF DICLOFENAC SODIUM IN TAIL VEIN OF WISTAR RAT

Diclofenac is the most popular and widely prescribed non-steroidal anti-inflammatory drug (NSAID). However, no preclinical data are available on repeated diclofenac IV bolus injection. In the present study, forty male Wistar rats were randomly divided in in total of four groups with 10 rats in each group. The control group received 0.9% sodium chloride injection. Marketed injectable Diclofenac Sodium formulations of Jonac AQ (75 mg/mL), Dynapar AQ (75 mg/mL) and Voveran (75 mg/mL) were administered in group 2, 3 and 4 respectively @ 15.4 mg/kg body weight as IV bolus injection daily for seven days in the lateral tail vein. At the end of seven days treatment period, six animals per group were sacrificed. The remaining four animals per group were sacrificed after seven days recovery period. On day 8 of the study, 9/10 rats in the Voveran group, 10/10 rats in the Dynapar AQ group and 6/10 rats in Jonac AQ group showed an injection site reaction. On day 15 (reversal necropsy) of the study, 4/4 rats in Voveran group, 4/4 rats in the Dynapar AQ group and 3/4 rats in Jonac AQ group showed injection site reaction. Microscopically, intravenous injection of Jonac AQ, Dynapar AQ and Voveran induced necrosis of tail skin, thrombosis and/or thrombophlebitis, degeneration/regeneration of skeletal muscles and subcutaneous fibrosis of variable severity. In conclusion, macroscopically and microscopically, among all three marketed Diclofenac Sodium injections, Voveran group caused more severe local reaction followed by the Dynapar AQ group while Jonac AQ injection was better tolerated and revealed less severe reaction at the local injection site.