Pharmacology, safety, efficacy and clinical uses of the COX‐2 inhibitor robenacoxib

Abstract

Robenacoxib is a non-steroidal anti-inflammatory drug (NSAID) of the coxib class. The coxibs were introduced with the objective of selectively inhibiting the cyclooxygenase-2 (COX-2) isoform of COX. COX-1 is present in many tissues constitutively and has several protective functions, including gastric cytoprotection, regulation of renal blood flow and regulation of platelet activity, whilst COX-2 is mainly induced locally and for restricted periods, and is primarily responsible for pain and inflammation (Pairet & Engelhardt, 1996). Drugs that inhibit COX-2 but spare COX-1 were therefore designed to have improved safety margins, especially for the gastrointestinal tract (Flower, 2003).

Robenacoxib pharmacokinetics in sheep following oral, subcutaneous, and intravenous administration

“…In sheep (1.5 h), rats (1 h, King et al, 2009 ), dogs (0.5 h, Schmid, Spreng, et al, 2010 ; Borer et al, 2017 ), and cats (0.5 h; King et al, 2013 ), T max was relatively short after oral administration. These data, alongside the relatively short half‐life, are consistent with rapid absorption (Lees et al, 2022 ). Orally administered RX should be rapidly absorbed from the rumen, given its relatively high aqueous solubility of 0.17 g/L at a pH between 6.4 and 6.8.…”

“…To note that, in dogs, RX has a longer duration (>24 h) of effect in illnesses involving peripheral inflammation due to its selectivity for inflammatory sites. This made RX suitable to be given to dogs once a day, despite what its short blood half-life would suggest (Lees et al, 2022).…”

“…However, at a RX concentration of 2 μg/ml, protein binding exceeded 98% in dogs and cats (Jung et al, 2009). Furthermore, since the Vss value is similar to the sheep's blood volume which is 0.075 L/kg (Luethy et al, 2017), a plasma protein binding study would be also useful to assess whether the drug tends to remain in the extra-or intra-cellular compartment, since it TA B L E 1 Mean pharmacokinetic parameters and range in sheep (n = 5) after single IV (2 mg/kg), SC (4 mg/kg), and PO (4 mg/kg) doses of robenacoxib is an important factor to assess the drug efficacy (Lees et al, 2022).…”

“…However, at a RX concentration of 2 μg/ml, protein binding exceeded 98% in dogs and cats (Jung et al, 2009 ). Furthermore, since the Vss value is similar to the sheep's blood volume which is 0.075 L/kg (Luethy et al, 2017 ), a plasma protein binding study would be also useful to assess whether the drug tends to remain in the extra‐ or intra‐cellular compartment, since it is an important factor to assess the drug efficacy (Lees et al, 2022 ). In fact, the selective distribution of RX to sites of inflammation has been demonstrated in rats, dogs, and cats and is attributable to its physicochemical property as a weak acid (pKa 4.7).…”

“…Among this class, robenacoxib (RX) is a highly selective COX‐2 inhibitor and is registered as injectable and flavored tablet formulations for dogs and cats (EMA, 2008 ). In all the targeted species and at clinically recommended dosages, no significant COX‐1 inhibition was observed (in vitro IC50 ratios COX‐1:COX‐2, 129:1 in dogs, 32:1 in cats) (Lees et al, 2022 ; Schmid, Seewald, et al, 2010 ). Animal species other than dogs and cats, such as sheep, could potentially benefit from this drug.…”