Researchers have successfully evaluated the pharmacokinetic and tolerability profiles of carprofen, a widely used nonsteroidal anti-inflammatory drug (NSAID), for treating pain in laboratory rats. The study aimed to identify the most effective and least invasive methods for administering this drug, finding promising results for both subcutaneous injection and oral self-administration.
The main emphasis of the study was to refine analgesia techniques to improve animal welfare and reduce pain during experiments, adhering to the 3R principles. The research involved 55 Sprague Dawley rats, consisting of 28 males and 27 females, which underwent various assessments to gauge the effectiveness and safety of carprofen.
Carprofen was administered through two methods: via subcutaneous injection of 5 mg/kg and through drinking water at 10 mg/kg/24 h. Blood samples were collected at various intervals to analyze plasma concentrations and track the drug's elimination half-life. After the subcutaneous injection, the maximum plasma concentration (Cmax) reached 39.16 ± 7.38 µg/ml at 3 hours, demonstrating prolonged therapeutic effects with levels remaining above the estimated effective threshold for at least 6 hours.
Oral administration via drinking water was well-accepted by the rats, leading to stable plasma concentrations throughout the 5-day treatment period. At 24 hours, the expected plasma concentration was also achieved, with levels peaking at 38.68 ± 8.67 µg/ml. This method of drug delivery proved to be both practical and less stressful for the rats, offering a potential avenue for improving pain management protocols.
The researchers evaluated the tolerability and potential side effects of carprofen using modified Irwin test parameters, including general activity, body temperature, and behavioral changes. While mild and transient side effects were observed, such as slight sedation and decreased body temperature among female rats, no significant gastrointestinal issues were reported. This reinforces the drug's safety profile for laboratory use.
Another significant outcome arose from the evaluation of behavioral indicators traditionally used to assess pain, such as burrowing and nesting activities. The study found no substantial impact from carprofen treatment on these behavioral markers, ensuring the reliability of such indicators for future research settings.
Overall, the findings support the stability and efficacy of carprofen as a practical analgesic for laboratory rats, highlighting its potential for both subcutaneous and oral administration. Such advancements stand to improve pain management standards within the domain of animal research, aligning with ethical principles aimed at enhancing animal welfare.