Disposition of firocoxib in late pregnant and early postpartum mares

Abstract

Pregnancy induces several physiologic changes that might impact the bioavailability, distribution, metabolism, and excretion of drugs. The objective of this study was to determine the effects of pregnancy on the disposition of oral firocoxib in mares. Seven pony mares received oral firocoxib paste at a dose of 0.1 mg/kg during late pregnancy and again 12 to 33 days postpartum. Firocoxib concentrations were measured in plasma by HPLC with ultraviolet detection. Maximum plasma concentrations were significantly lower in pregnant (50.0 ± 21.8 ng/mL) than in postpartum (73.7 ± 25.6 ng/mL) mares. Plasma concentrations 24 h after administration, time to maximum plasma concentrations, and area under the plasma concentration versus time curve were not significantly different between late pregnancy and the postpartum period in mares.

Serum Disposition of a Single Dose of Orally Administered Firocoxib in African Elephants (Loxodonta Africana)

“…Firocoxib has been extensively evaluated in domestic animals with pharmacokinetic, 18,23,24,29,38,41,57,65 COX isoenzyme inhibition, 13,20 efficacy, 2,3,19,39,47,53 and drug safety/drug interaction 17,30,34,56 studies proving the specificity for the COX-2 isoenzyme and efficacy of this drug for management of chronic conditions, such as osteoarthritis. The published adverse effects of firocoxib appear to be minimal in domestic dogs 2 and horses 47 but do include unusual descriptions in zoo animals, such as the development of bullous skin lesions in a white rhinoceros 58 and possible dermatitis in a hippopotamus.…”

“…7,25,26,28 While these similarities may warrant comparison, differences in drug metabolism demonstrate a need for pharmacokinetic studies in elephants, especially for nonsteroidal anti-inflammatory drugs (NSAIDs), which may be administered frequently or for long periods of time. 4,6,21,27,36,42 Firocoxib has been extensively evaluated in d o m e s t ic a n i m a ls w i th p h a r m a c okin e tic, 18,23,24,29,38,41,57,65 COX isoenzyme inhibition, 13,20 efficacy, 2,3,19,39,47,53 and drug safety/drug interaction 17,30,34,56 studies proving the specificity for the COX-2 isoenzyme and efficacy of this drug for management of chronic conditions, such as osteoarthritis. The published adverse effects of firocoxib appear to be minimal in domestic dogs 2 and horses 47 but do include unusual descriptions in zoo animals, such as the development of bullous skin lesions in a white rhinoceros 58 and possible dermatitis in a hippopotamus.…”

Ancillary treatment to support pregnancy in cases of medical disease

“…Recently, the primarily COX‐2‐selective anti‐inflammatory firocoxib has been investigated in the pregnant mare (Giguère et al., 2016; Macpherson et al., 2021) as firocoxib ideally has less deleterious effects on the gastrointestinal and renal systems. Initial work illustrated no adverse effects in mares treated with daily oral firocoxib at 0.1 mg/kg bwt, but the maximum concentration of the drug was significantly lower in pregnant mares (Giguère et al., 2016).…”

“…Recently, the primarily COX‐2‐selective anti‐inflammatory firocoxib has been investigated in the pregnant mare (Giguère et al., 2016; Macpherson et al., 2021) as firocoxib ideally has less deleterious effects on the gastrointestinal and renal systems. Initial work illustrated no adverse effects in mares treated with daily oral firocoxib at 0.1 mg/kg bwt, but the maximum concentration of the drug was significantly lower in pregnant mares (Giguère et al., 2016). As firocoxib has a long half‐life, the authors proposed that a steady state in pregnant mares could be reached by using a loading dose of 0.3 mg/kg bwt followed by 0.1 mg/kg bwt by mouth every 24 h akin to the practice performed in other musculoskeletal and gastrointestinal conditions in the horse (Cox et al., 2013; Giguère et al., 2016).…”

“…Initial work illustrated no adverse effects in mares treated with daily oral firocoxib at 0.1 mg/kg bwt, but the maximum concentration of the drug was significantly lower in pregnant mares (Giguère et al., 2016). As firocoxib has a long half‐life, the authors proposed that a steady state in pregnant mares could be reached by using a loading dose of 0.3 mg/kg bwt followed by 0.1 mg/kg bwt by mouth every 24 h akin to the practice performed in other musculoskeletal and gastrointestinal conditions in the horse (Cox et al., 2013; Giguère et al., 2016). Macpherson and colleagues (2021) followed this work by using the loading dose of 0.3 mg/kg bwt per os q.…”