A study of the pharmacokinetics and thromboxane inhibitory activity of a single intramuscular dose of carprofen as a means to establish its potential use as an analgesic drug in white rhinoceros

Abstract

The alleviation of pain and prevention of suffering are key aspects of animal welfare. Unfortunately, analgesic drugs are not available for all species. White rhinoceros (Ceratotherium simum), representing one of such species, which survive poaching attempts inflicted with severe facial injuries and gunshot wounds, nonetheless require analgesic support. To improve treatment conditions, this study explored the use of carprofen for the treatment of pain and inflammation in white rhinoceros. The pharmacokinetics of 1 mg/kg intramuscular carprofen was evaluated in six healthy white rhinoceros. The half-life of λ and mean residence time was 105.71 ± 15.67 and 155.01 ± 22.46 hr, respectively. The area under the curve and the maximum carprofen concentration were 904.61 ± 110.78 μg ml hr and 5.77 ± 0.63 μg/ml, respectively. Plasma TXB inhibition demonstrated anti-inflammatory properties and indicated that carprofen may be effective for a minimum of 48 hr in most animals. With its long half-life further indicating that a single dose could be effective for several days, we suggest that carprofen may be a useful drug for the treatment of white rhinoceros.

Phylogenetic analysis of the cytochrome P450 (CYP450) nucleotide sequences of the horse and predicted CYP450s of the white rhinoceros (Ceratotherium simum) and other mammalian species

“…To overcome limitations in species specific information, the medical management of the rhino tends to be based on information available for the horse. However, the findings of a recent study we undertook in rhinos showed that the half-life of elimination for carprofen was more than threefold longer than that in the horse ( Leiberich et al, 2018 ). This made us question the validity of the horse as a model.…”

“…While from a general phylogenetic point of view the horse is regarded as one of the closest related species to the rhinoceros ( Tougard et al, 2001 ), we questioned whether it is correct to treat rhinos like large horses. Studies ( Leiberich et al, 2018 ; M. Leiberich, 2018, unpublished data) have recently been undertaken in order to elucidate this issue. Enrofloxacin and carprofen, two potential drugs for the antimicrobial and analgesic treatment of poaching victims and other injured white rhinos, were evaluated in plasma pharmacokinetic studies.…”

“…These studies revealed significant differences between drug pharmacokinetic parameters in the white rhino and the horse. Carprofen was characterised by a half-life of elimination of 105.71 ± 15.67 h, which is by far the longest recorded for any animal species ( Leiberich et al, 2018 ). Furthermore, interspecies allometric scaling of enrofloxacin was able to show that the difference in the half-life of enrofloxacin in white rhino was not only due to the relative differences in their body size and that the half-life was not allometrically scalable (M. Leiberich, 2018, unpublished data).…”

Phenylbutazone pharmacokinetics in southern white rhinoceros (Ceratotherium simum simum) after oral administration

“…Approximately, 18,000 southern white rhinoceros ( Ceratotherium simum simum , SWR) inhabit wild and semi‐wild environments (Emslie et al, 2019) as an important apex consumer in the savannas of southern Africa (Cromsigt & te Beest, 2014; Emslie et al, 2019). These wild populations have been declining since 2012 due to increased poaching (Emslie et al, 2019), and each year approximately 200 to 300 SWR are found alive after poaching attacks, often with gunshot wounds or wounds to their frontal and nasal bones (Leiberich et al, 2018). Appropriate medical management of these injuries following systemic stabilization includes wound lavage and effective analgesia (Meyer et al, 2015).…”

“…Only two NSAIDs, carprofen (Leiberich, Krebber, et al, 2018) and flunixin meglumine (East et al, 2019), have been investigated for use in rhinoceros. A single 1 mg/kg intramuscular injection in SWR of carprofen reduced thromboxane B 2 activity for 48 h and had an elimination half-life (T 1/2 ) of 106 h, which is the longest reported T ½ for that drug in any mammalian species (Leiberich, Krebber, et al, 2018). The T 1/2 of a single oral dose of flunixin meglumine in SWR was determined to be approximately 8 h, which is over 5 times the T ½ of the same dose reported in horses (East et al, 2019).…”