Pharmacokinetics and local tolerance of cefovecin sodium after intra‐articular administration in horses

Abstract

Searching for new therapeutic options against septic arthritis in horses, this research was focused on the study of the kinetics and local side effects after the intra-articular treatment of horses with cefovecin sodium. A single dose (240 mg) of the drug (Convenia ) was administered into the radiocarpal joint of adult healthy horses (n = 6), and drug concentrations in plasma and synovial fluid were determined by high-performance liquid chromatography (HPLC). Local tolerance was also studied based on the modification of different joint physiopathological parameters (pH, cellular, and protein concentration in synovial fluid). Although no clinically relevant joint damage was noticed, significant increases in the protein concentrations at 5 min and in the cellular concentration at 30 min after cefovecin administration were observed in the treated radiocarpal joints. The duration of the cefovecin above the minimal inhibitory concentration (MIC) ≤1 μg/mL was 28.80 ± 2.58 h in the radiocarpal joint and 16.00 ± 2.86 h in plasma. The results of this study showed that intra-articular administration of cefovecin sodium in horses could be considered in the future to manage septic arthritis in horses, as it offers a good pharmacokinetic behavior and good local tolerance.

Intra‐articular administration of antibiotics in horses: Justifications, risks, reconsideration of use and outcomes

“…43 Finally, both tobramycin and cefovecin sodium (dosed at 240 mg in the radiocarpal joint in both studies) induced mild chemical synovitis evidenced by increased nucleated cell counts and total protein in synovial fluid, although it was concluded that no clinically relevant joint damage occurred. 39,44 The long-term effects of antibiotic-induced synovitis have not been evaluated at this time to the authors' knowledge, and therefore it is unknown to what extent IA antibiotic usage may contribute to the long-term progression of osteoarthritis within the injected joint (Table 2).…”

“…Pharmacokinetic distribution of antibiotics following IA injection has been explored for aminoglycosides, ceftiofur sodium and cefovecin sodium. 20,39,40,[44][45][46] When the IA route of administration was compared with regional limb perfusion, gentamicin (one gram injected by either route) reached higher peak concentrations in synovial fluid following IA injection, but did not differ in serum or bone. 45 Amikacin concentrations were lower and distribution of amikacin (500 mg) from radiocarpal joints occurred more rapidly (48 vs 72 hours) from endotoxin-inflamed vs normal joints.…”

“…20,39 Cefovecin sodium (240 mg in the radiocarpal joint) remained above 1 µg/mL in synovial fluid for over 24 hours. 44 The co-authors recently further investigated and compared the effects of IA amikacin injected at a range of doses on synovial fluid drug concentrations and biomarkers of cartilage injury and inflammation using horse models in vivo. 40 In contrast to reported findings with aminoglycosides, no differences in histologic scoring of synovium and cartilage or synovial fluid cytological parameters were observed following ceftiofur sodium (150 mg) injection in the antebrachiocarpal joint.…”

In vitro binding of cefovecin to plasma proteins in Australian marsupials and plasma concentrations of cefovecin following single subcutaneous administration to koalas (Phascolarctos cinereus)

“…3,4 Some information about cefovecin's pharmacokinetic (PK) profile is available for some non-human primates, 5-7 hens, 8 alpacas, 9 some aquatic species, 10-12 other non-domesticated species [13][14][15] and some limited information is available for the horse. 16,17 Cefovecin has a long elimination half-life in the cat and dog (≈ 7 and 5 days, respectively); 3,4 furthermore a single SC injection of 8 mg/kg body weight reportedly has antimicrobial activity in plasma and transudates between 10 and 14 days in these species. 3,4 The long elimination half-life of cefovecin has been attributed to the high proportion of plasma protein binding (PPB) in dogs, cats and monkeys (> 90%).…”