Abstract
Cefovecin is a third-generation cephalosporin developed by Pfizer Animal Health as an aqueous solution for veterinary use by subcutaneous route (8 mg/kg) in dogs and cats. In vitro activity of the drug against all major aerobic and anaerobic bacterial pathogens (gram-positive and gram-negative) in pets has been demonstrated.1 The pharmacokinetic behavior of cefovecin in dogs and cats is characterized by a long elimination half-life and activity in transudate for up to 2 weeks,2,3 making it suitable for antibacterial treatment with a 14-days dosing interval in these species. The pharmacological properties of this antibiotic may be an advantage for the exotic veterinary medicine field due to the convenience of its broad-spectrum, administration route and long duration of activity (long half elimination life) which overall allows minimal handling and therefore stress. It has led several veterinarians to an empirical off-label use of cefovecin in other animal species.4 The aim of the present study is to evaluate the pharmacokinetic behavior of cefovecin in dolphin (Tursiops truncatus) and sea lion (Otaria flavescens) after intramuscular administration in order to determine if there is any advantage for its use in these species. During the study, three Patagonian sea lions and two bottle nose dolphins (one dolphin from the Oceanográfic in Valencia and one one-day-old dolphin from Zoomarine in Portugal) were intramuscularly injected with ConveniaTM (cefovecin, 8 mg/kg for all sea lions and the adult dolphin and 6.7 mg/kg for the dolphin neonate). Blood samples were collected prior to injection (t = 0) and then serially along 60 days. Plasma concentrations of the drug were determined by validated HPLC methods with UV detection, and pharmacokinetic parameters were calculated using a non-compartmental analysis. In sea lions, the mean peak plasma concentration (55.21 µg/ml) occurs at 8 hours, and the drug concentrations lasted over the MIC90 (minimum inhibitory concentration: for Staphylococcus intermedius, 0.25 µg/ml; for Escherichia coli, 1.0 µg/ml) for longer than 53 days when the last sample was taken. In adult and neonate dolphins, the time for peak plasma level was similar (about 8 and 9 h, respectively) although the maximum drug concentration was different (79.19 and 35.49 µg/ml, respectively), possibly due to the cefovecin dose used. Drug concentrations remained over the MIC90 for 10.4 and 17 days respectively; and the elimination half-life values estimated were 3.5 and 8.5 days for neonate and adult dolphin, respectively; data were similar to those reported in dogs and cats (about 5.5 and 7 days, respectively).2,3 In sea lions, both elimination half-life (about 4 weeks) and mean residence time (about 32 days) were longer than those previously published for pets2,3 and considerably longer than in birds and reptiles.4 In conclusion, cefovecin, administered intramuscularly to dolphins and sea lions, seems to present a good pharmacokinetic profile and so, it could be considered to provide benefits over the alternative broad-spectrum antimicrobials currently used in these species. Attending to the pharmacokinetic properties, the administration dosing intervals for cefovecin in Patagonian sea lions should be clearly wider than those recommended for pets. Additionally, in sea lions dosages lower than 8mg/kg could be considered in order to shorten the duration of treatment.
Acknowledgements
The authors would like to acknowledge Pfizer Salud Animal for their support on this study, as well as all the biology department of the Oceanográfic and Zoomarine for their great effort in animal training, allowing to sample the animals routinely to obtain the antibiotic kinetic curves.
References
1. Stegemann MR, Pasmore CA, Sherington J, Lindeman CJ, Papp G, Wigl DJ, Skogerboe TL 2006. Antimicrobial activity and spectrum of cefovecin, a new extended spectrum cephalosporin, against pathogens collected from dogs and cats in Europe and North America. Antimicrob Agents Chemother 50:2286-2292.
2. Stegemann MR, Sherington J, Blanchfloser S 2006. Pharmacokinetics and pharmacodynamics of cefovecin in dogs. J Vet Pharmacol Ther 29:501-511.
3. Stegemann MR, Sherington J, Coati N, Brown SA, Blanchflower S 2006. Pharmacokinetics of cefovecin in cats. J Vet Pharmacol Ther 29:513-524.
4. Thuesen LR, Bertelsen MF, Brimer L, Skaanild MT. 2009. Selected pharmacokinetic parameters for Cefovecin in hens and green iguanas. J Vet Pharmacol Ther 32:613-617.