Does Phylogeny Influence the Determination of Drug Dosages by Allometric Scaling?
Jean-Michel Hatt, Dr med vet, MSc, DACZM, DECZM (Avian); Lukas Kenel, med vet; Marcus Clauss, Dr med vet, MSc, DECVCN
When treating animals, zoo veterinarians often face the challenge that the correct dosage and dosage regimen has not been scientifically determined for the species in question. Therefore, the clinician will either extrapolate dosages from other, typically domestic, species or refer to predictions by allometric scaling. Conventional allometric scaling shares the assumption that interspecies differences are clinically negligible. In the present study we tested the assumption about interspecies differences with respect to phylogenetic relationship in mammals. We collated data from studies that investigated intravenous application of enrofloxacin on steady state distribution volume, total body clearance, and elimination half-life, and that also provided the body mass of the investigated animals. A total of 55 references involving 17 species were used to calculate species averages. These data were log-transformed and submitted to linear regression, first using ordinary least squares (without accounting for phylogeny), and, after linking to an established phylogenetic tree for mammals, to phylogenetic-generalized least squares. The phylogenetic signal in the dataset was evaluated and estimated to not be significantly different from zero (i.e., no detectable phylogenetic structure in the data). While half-life was not significantly correlated to body mass, both steady state volume and clearance scaled at body mass0.80, with the metabolic exponent of 0.75 included in the 95% confidence interval in both cases. Even though species differences have been described beyond the influence of allometry, the data evaluation does not suggest a systematic effect of phylogenetic affiliation.