Pharmacokinetics of cefovecin in cats

Abstract

The pharmacokinetics of the novel cephalosporin cefovecin were investigated in a series of in vivo, ex vivo and in vitro studies following administration to adult cats at 8 mg/kg bodyweight. Bioavailability and pharmacokinetic parameters were determined in a cross-over study after intravenous (i.v.) and subcutaneous (s.c.) injections. [14C]cefovecin was used to evaluate excretion for 21 days after s.c. administration. Protein binding was determined in vitro in feline plasma and ex vivo in transudate from cats surgically implanted with tissue chambers. After s.c. administration, cefovecin was characterized by rapid absorption with mean peak plasma concentrations of 141+/-12 microg/mL being achieved within 2 h of s.c. injection with full bioavailability (99%). The mean elimination half-life was 166+/-18 h. After i.v. administration, volume of distribution was 0.09+/-0.01 L/kg and mean plasma clearance was 0.35+/-0.04 mL/h/kg. Approximately 50% of the administered radiolabelled dose was eliminated over the 21-day postdose period via urinary excretion and up to approximately 25% in faeces. In vitro and ex vivo plasma protein binding ranged from 99.8% to 99.5% over the plasma concentration range 10-100 microg/mL. Ex vivo protein binding in transudate was as low as 90.7%. From 8 h postdose, concentrations of unbound (free) cefovecin in transudate were consistently higher than in plasma, with mean unbound cefovecin concentrations being maintained above 0.06 microg/mL (MIC90 of Pasteurella multocida) in transudate for at least 14 days postdose. The slow elimination and long-lasting free concentrations in extracellular fluid are desirable pharmacokinetic attributes for an antimicrobial with a 14-day dosing interval.

CEFOVECIN (CONVENIA) FOR THE TREATMENT OF SEPTIC PERITONITIS IN A FEMALE LION (PANTHERA LEO)

“…8 The animal was given meloxicam (Metacam, Boehringer Ingelheim, St. Joseph, Missouri 64506, USA; 0.2 mg/kg subcutaneously) for postoperative analgesia. The lion was moved to a rolling menagerie cage and given atipamezole (Antise- dan, Pfizer Animal Health; 0.12 mg/kg i.m.)…”

Resisting the resistance. Is there progress in maintaining antimicrobial efficacy?

“…An example is cefovecin. This drug reaches very good serum concentrations 24,25 but has high protein binding, which reduces the amount of free drug and thus antimicrobial activity. This gives rise to concerns, as the free drug concentration remains in the MSW for an extended period of time.…”

Cefovecin: A New Long-acting Cephalosporin

“…It is rapidly and nearly completely absorbed from the subcutaneous injection site, with a bioavailability of 99% in dogs and cats [2]. Another factor is the high plasma protein binding of 96-98.7% in dogs [15] and more than 99% in cats [16]. A third, important factor is the fact that only the free drug is eliminated, primarily via the kidneys [2].…”

“…Studies about the therapeutic use of cefovecin have been conducted on cats, dogs, hens, green iguanas and ferrets [15][16][17]19,[23][24][25][26][27][28]. Besides, brief elimination studies have been performed in 4 species of ruminants, 2 species of primates, 3 species of exotic felids, ring tailed lemurs and in the domestic pig [40].…”

“…Besides, brief elimination studies have been performed in 4 species of ruminants, 2 species of primates, 3 species of exotic felids, ring tailed lemurs and in the domestic pig [40]. In cats, cefovecin is approved for use at a single subcutaneous injection of 8 mg/kg with a 14 days dosing interval if clinically indicated [16].…”