Pharmacokinetics of intravenous and subcutaneous cefovecin in alpacas

Abstract

The purpose of this study was to determine the pharmacokinetics of cefovecin after intravenous and subcutaneous dose of 8 mg/kg to alpacas. Bacterial infections requiring long-term antibiotic therapy such as neonatal bacteremia, pneumonia, peritonitis, dental, and uterine infections are a significant cause of morbidity and mortality in this species. However, few antimicrobials have been evaluated and proven to have favorable pharmacokinetics for therapeutic use. Most antimicrobials that are currently used require daily injections for many days. Cefovecin is a long-acting cephalosporin that is formulated for subcutaneous administration, and its long-elimination half-life allows for 14-day dosing intervals in dogs and cats. The properties of cefovecin may be advantageous for medical treatment of camelids due to its broad spectrum, route of administration, and long duration of activity. Pharmacokinetic evaluation of antimicrobial drugs in camelids is essential for the proper treatment and prevention of bacterial disease, and to minimize development of antibiotic resistant bacterial strains due to inadequate antibiotic concentrations. Cefovecin mean half-life, volume of distribution at steady-state, and clearance after intravenous administration were 10.3 h, 86 mL/kg, and 7.07 mL·h/kg. The bioavailability was 143%, while half-life, C(max), and T(max) were 16.9 h, 108 μg/mL, and 2.8 h following subcutaneous administration. In the absence of additional microbial susceptibility data for alpaca pathogens, the current cefovecin dosage regimen prescribed for dogs (8 mg/kg SC every 14 days) may need to be optimized for the treatment of infections in this species.

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

“…29,30 It has been reported that the actual observed unbound proportions of various β-lactam antibiotics can be highly variable in ill people. 3,4 This current study and several others demonstrate a wide interspecies PPB variance, such as 69-91% in alpacas, 9 37.9-50.2% in Hermann's tortoises 13 and 78% in sea otters. 32 It is also important to recognise that high PPB is not indicative of a long elimination half-life; PPB is just one of many factors that may influence drug disposition.…”

“…33 Cefovecin has been demonstrated to have a slow elimination in the cat and dog because it combines high protein binding with a relatively low clearance. 3,4 This current study and several others demonstrate a wide interspecies PPB variance, such as 69-91% in alpacas, 9 37.9-50.2% in Hermann's tortoises 13 and 78% in sea otters. 12 Likewise, the cefovecin elimination rate has been shown to be more variable across species, with the half-life ranging from 136 AE 12 h in the dog to 8.5 AE 0.78 h in baboons.…”

“…12 Likewise, the cefovecin elimination rate has been shown to be more variable across species, with the half-life ranging from 136 AE 12 h in the dog to 8.5 AE 0.78 h in baboons. 3,4,6,7,9 However, as the cefovecin elimination rate is most variable between species, it is most likely that cefovecin has a fast clearance in the koala. The low cefovecin concentrations detected in live koalas were unexpected and resulted in limited pharmacological information.…”

“…34 The Vd ss reported for many species appears more consistent and approximates 1 L/kg. 3,4,6,7,9 However, as the cefovecin elimination rate is most variable between species, it is most likely that cefovecin has a fast clearance in the koala.…”

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

“…Some authors have attributed this property to the highly plasma protein binding that some domestic animals presented (e.g., 96–98.7% in dogs (Stegemann et al ., ) and >99% in cats (Stegemann et al ., )), and because only the free drug is eliminated mainly via the kidneys (EMEA, ). However, herbivores and some exotic animals have not reached the same therapeutic duration, having a much shorter half‐life in all the species that were investigated, independently of their antibiotic‐plasmatic protein binding (Thuesen et al ., ; Bertelsen et al ., ; Gilabert et al ., ; Montesinos et al ., ; Papp et al ., ; Cox et al ., ). Because of being impossible to emulate a similar dosing scheme as the ones proposed for dogs and cats, no studies of cefovecin in horses have been published.…”