Favorable pharmacokinetic and tolerability profiles make carprofen an attractive analgesic for subcutaneous injection and oral self-administration in rats

Aylina Glasenapp; Jens P. Bankstahl; Heike Bähre; Andrey Kozlov; Silke Glage; Marion Bankstahl

doi:10.1038/s41598-025-93336-3

You are here:

PHAIDRA
Detail o:4026

Title (eng)

Favorable pharmacokinetic and tolerability profiles make carprofen an attractive analgesic for subcutaneous injection and oral self-administration in rats

Author

Aylina Glasenapp

Jens P. Bankstahl

Heike Bähre

Andrey Kozlov

Silke Glage

Marion Bankstahl

University of Veterinary Medicine Vienna

Abstract (eng)

As basis for evidence-based analgesia refinement, species-specific pharmacokinetic and tolerability profiles of carprofen were determined in rats for least aversive administration routes and prolonged treatment. Further, potential influence on behavioral pain indicators was evaluated. LC-MS/MS determined plasma concentrations in Sprague-Dawley rats (n?=?21/sex) after subcutaneous (s.c.) injection (5 mg/kg) and during a 5-day treatment via the drinking water (d.w., 10 mg/kg/24 h). Irwin test parameters, clinical scoring, body weight, body temperature, fluid and food intake, grimace scale, burrowing, nesting, hematology, and histopathology were investigated. Plasma concentrations early after injection were higher in females, reached a maximum (Cmax) of 39.16?±?7.38 µg/ml at 3 h after injection and remained above an estimated in-vitro-derived therapeutic threshold (24.3 µg/ml) for at least 6 h with a T1/2 of 7.06 h. Carprofen-medicated d.w. was readily consumed, with constant target dose intake over the 5-day treatment period reaching a Cmax of 38.68?±?8.67 µg/ml at 24 h. Tolerability and behavioral parameters revealed only minor changes, such as transient sedation (s.c.) and decreased body temperature (females). Gastrointestinal adverse effects were not detected. Carprofen's pharmacokinetic profile allows for a practicable s.c. injection interval. Acceptance and tolerability during prolonged oral treatment with the assessed dose of 10 mg/kg/24 h makes its non-invasive administration promising for analgesia refinement in rats.

Keywords (eng)

AnimalsInjections, SubcutaneousRats, Sprague-DawleyRatsFemaleCarbazoles PharmacokineticsCarbazoles Administration & DosageCarbazoles Adverse EffectsAdministration, OralMaleAnalgesics PharmacokineticsAnalgesics Administration & DosageSelf AdministrationPaindrug Therapy

Type (eng)

journal article

Language

[eng]

Persistent identifier

https://phaidra.vetmeduni.ac.at/o:4026

DOI

10.1038/s41598-025-93336-3

Is in series

Title (eng)

Scientific Reports

Volume