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

Abstract

Background Cefovecin has a long duration of antibiotic activity in cats and dogs, somewhat attributable to its high plasma protein binding. Aims To determine the cefovecin binding to plasma proteins in vitro in selected Australian marsupials and to quantify the change in cetovecin concentration over time following subcutaneous injection in koalas. Methods and results Various cefovecin concentrations were incubated with plasma and quantified using HPLC. The median (range) bound percentages when 10 μg/mL of cefovecin was incubated with plasma were 11.1 (4.1–20.4) in the plasma of the Tasmanian devil, 12.7 (5.8–17.3) in the koala, 18.9 (14.6–38.0) in the eastern grey kangaroo, 16.9 (15.7–30.2) in the common brush‐tailed possum, 37.6 (25.3–42.3) in the eastern ring‐tailed possum and 36.4 (35.0–38.3) in the red kangaroo, suggesting that cefovecin may have a shorter duration of action in these species than in cats and dogs. Cefovecin binding to plasma proteins in thawed, frozen equine plasma was also undertaken for assay quality control and the median (range) plasma protein binding (at 10 μg/mL) was 95.6% (94.9–96.6%). Cefovecin was also administered to six koalas at 8 mg/kg subcutaneously and serial blood samples were collected at 3, 6, 24, 48, 72, 96 h thereafter. Cefovecin plasma concentrations were not quantifiable in four koalas and in the other two, the mean plasma concentration at t = 3 h was 1.04 ± 0.01 μg/mL. Conclusion Because of the limited pharmacokinetic data generated, no further pharmacokinetic analysis was performed; however, a single injected bolus of cefovecin is likely to have a short duration of action in koalas (hours, rather than days).

Pharmacokinetic profile of injectable tramadol in the koala (Phascolarctos cinereus) and prediction of its analgesic efficacy

“…Tramadol, M1 and M2 binding to plasma protein was undertaken with thawed / frozen koala plasma which has limitations [ 30 , 31 ]. Generally, tramadol’s binding to human plasma proteins is approximately 20% [ 12 ] and the bound fraction of M1 to human plasma proteins can be as high as 80% [ 25 ], similar to that observed with koala plasma proteins.…”

Assay validation and determination of in vitro binding of mefloquine to plasma proteins from clinically normal and FIP-affected cats

“…In humans, mefloquine is also highly plasma protein bound (> 98%) [14], which may account, in part, for its long half-life of approximately three weeks in healthy human subjects [24]. High plasma protein binding can result in the drug-protein complex acting as a reservoir for the physiologically active free drug concentration and consequently prolonging its duration of action [12,25]. Likewise, it should not be assumed that a drugs' PPB is constant across species [25].…”

“…High plasma protein binding can result in the drug-protein complex acting as a reservoir for the physiologically active free drug concentration and consequently prolonging its duration of action [12,25]. Likewise, it should not be assumed that a drugs' PPB is constant across species [25]. In a comparative species study investigating the plasma protein binding of 574 compounds, drugs tend to be slightly more bound in human plasma proteins in comparison to the plasma proteins of rats, mice and dogs [26].…”

In this issue – March 2019: Clinical review of feline viral diagnosis · Vaccination reactions in experimental sheep · Swimming excercise in Standardbreds · Bone fragments in young Thoroughbreds · Cefovecin in marsupials · Mycobacteriosis in captive brolgas

“…5 The plasma binding in the marsupials ranged from 11% to 36% compared with 95.6% in the horse plasma that was used as a control. Cefovacin is a broadspectrum cephalosporin that has a long half-life in cats and dogs and was thought to be useful in Australian marsupials.…”

“…Because a long half-life is thought to be due to a combination of high plasma protein binding and renal reabsorption, the authors investigated plasma protein binding for Australian marsupials in vitro. 5 The plasma binding in the marsupials ranged from 11% to 36% compared with 95.6% in the horse plasma that was used as a control. They do note that their results in vitro may differ from that in the live animal and the plasma binding is only one factor that alters drug disposition and elimination rates of this drug have also been shown to vary widely.…”