Safety Assessment of a Novel Intravenous Diclofenac Sodium Formulation Following 28-Day Repeated Administration in Wistar Rats.
Int J Toxicol
; 43(5): 491-502, 2024.
Article
en En
| MEDLINE
| ID: mdl-38901831
ABSTRACT
These toxicity studies aimed to assess the safety and tolerability of a novel intravenous diclofenac sodium (37.5 mg/mL) formulation containing povidone K12 (80 mg/mL) as the key excipient in Wistar rats. This formulation was tested at doses of 3, 7, and 15 mg/kg/day and was administered daily for 28 days by intravenous route. Toxicokinetic estimation revealed a dose-proportional increase in plasma exposure to diclofenac. The formulation was well tolerated in males; however, mortality was observed in females (2/15) at the highest dose (15 mg/kg/day). Adverse gastrointestinal events related to NSAIDS and a few other treatment-related effects on clinical and anatomic pathology were noted at the 15 mg/kg/day dose, which normalized at the end of the 2-week recovery period. In addition, the excipient povidone K12 was present in a higher amount than the approved Inactive Ingredient Database (IID) limit in the proposed novel formulation. It was qualified through a separate 28-day repeated dose toxicity study by intravenous route in Wistar rats. Povidone K12 was found to be well tolerated and safe up to a dose of 165 mg/kg/day. No treatment-related adverse effects were observed in this study. In conclusion, repeated administration of a novel intravenous formulation containing diclofenac sodium was found to be safe up to the dose of 7 mg/kg/day in female rats and 15 mg/kg/day in male rats.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Antiinflamatorios no Esteroideos
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Diclofenaco
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Ratas Wistar
Límite:
Animals
Idioma:
En
Revista:
Int J Toxicol
/
Int. j. toxicol
/
International journal of toxicology
Asunto de la revista:
TOXICOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
India