Evaluation of allometric scaling as a tool for extrapolation of the enrofloxacin dose in American black vultures (Coragyps atratus)

Abstract

OBJECTIVE To determine the pharmacokinetics of enrofloxacin after IV administration in American black vultures (Coragyps atratus), to compare clearance of enrofloxacin in American black vultures with clearance of this fluoroquinolone in other avian species, and to evaluate whether allometric scaling is an appropriate tool for dose extrapolation in avian species. ANIMALS 6 healthy adult American black vultures. PROCEDURES Enrofloxacin concentrations were quantified by use of high-performance liquid chromatography. Pharmacokinetics of enrofloxacin was determined in American black vultures after IV administration. Pharmacokinetic parameters for 12 avian species obtained from 24 pharmacokinetic studies were used. Allometric analysis of enrofloxacin pharmacokinetic parameters was performed. RESULTS Volume of distribution at steady state for enrofloxacin was 3.47 L/kg, clearance was 0.147 L/h·kg, and elimination half-life was 18.3 hours. Comparisons among avian species revealed that American black vultures had the lowest extraction ratio for enrofloxacin (1.04%). Only the volume of distribution at steady state and clearance had a good allometric fit. Goodness of fit was improved when ratites were not included in the analysis. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that the use of allometric scaling for the prediction of volume of distribution at steady state could provide a suitable method for extrapolation of enrofloxacin doses among avian species; however, allometric scaling could not be used to adequately predict the clearance of enrofloxacin.

Pharmacokinetics of tolfenamic acid after different administration routes in geese (Anser cygnoides)

“…Mean absorption time (MAT) was calculated as MRT IM , SC , oral – MRT IV . The body extraction ratio ( E body ) for tolfenamic acid after IV administration is calculated using Cl T /QC (Toutain & Bousquet‐Melou, 2004), and QC (ml kg −1 min −1 ) is the cardiac output calculated according to the allometric equation with 290.7 × body weight (in kg) 0.69 (Grubb, 1983; Waxman et al, 2019).…”

Pharmacokinetic Behaviour of Enrofloxacin after Single Intramuscular Dosage in American Black Vultures (Coragyps atratus)

“…After intramuscular administration, enrofloxacin showed a rapid and complete absorption, reaching high Cmax and AUC values. Taking into account AUC values from previously published data on intravenously administered enrofloxacin to black vultures [ 8 ], a bioavailability value of 90% is estimated. This finding is in agreement with values described in other avian species, which oscillated between 90% and 99% [ 13 , 18 , 19 , 20 , 21 ].…”

“…If AUC is corrected by the administered dose (AUC/D), in general, birds of prey show high values, black vultures showing the highest one (vultures 7.39; great horned owls 4.35, red tailed hawks 3.60; caracaras 3.44 kg h/L), while ratites show very low values [ 22 , 23 , 24 ]. These findings could be related to a slow enrofloxacin clearance and a low extraction ratio observed in vultures after intravenous administration [ 8 ]. This behaviour could also be related to a long enrofloxacin permanence in black vultures, since elimination half-life showed values higher than 18 h. Compared to other avian species, we observed that vultures present the longest body permanence, with an elimination half-life almost double that observed in chickens (10.6 h) [ 19 ], and is almost 20 times longer than in ostriches [ 21 ].…”

“…This route could represent an interesting alternative to oral administration, in as much as anorexia, regurgitation and emesis have been observed in these species frequently after oral administration of enrofloxacin [ 6 ]. Different pharmacokinetic behaviour has been observed in vultures compared to other birds due to a slow elimination of drugs, such as fluroquinolones [ 7 , 8 ] or diclofenac [ 9 ]; however, empirical dosage, recommended for other species, is used for black vultures [ 10 ]. Dose extrapolation by linear, metabolic, or allometric scaling has limitations and, ideally, dosage recommendations should be based on species-specific pharmacokinetic and pharmacodynamic studies [ 11 , 12 ].…”

Pharmacokinetics and bioavailability of danofloxacin in swan geese (Anser cygnoides) following intravenous, intramuscular, subcutaneous, and oral administrations

“…Plasma concentrations of danofloxacin from each goose were analyzed with a non-compartmental analysis using WinNonlin The body extraction ratio (E body ) for danofloxacin after IV administration was calculated using Cl T /QC (Toutain & Bousquet-Melou, 2004), and QC (mL/kg/min) was the cardiac output calculated according to the allometric equation with 290.7 × body weight (in kg) 0.69 (Grubb, 1983;Waxman et al, 2019).…”