A study of the population pharmacokinetics of diminazene in dogs naturally infected with Babesia canis

Abstract

Diminazene is a drug that is commonly used in the treatment of canine babesiosis. Most of the pharmacokinetic work on diminazene has been undertaken in healthy individuals, while the influence of disease on diminazene pharmacokinetics has been investigated to a limited degree. Population pharmacokinetics allows for the investigation of factors (covariates) that influence pharmacokinetic parameters. The aim of this study was to provide a descriptive model of the population pharmacokinetics of intramuscularly administered diminazene in dogs naturally infected with Babesia canis. Thirty-nine dogs had 142 plasma samples collected. Another 56 samples from 8 healthy dogs, from a previous study, were added to the data set. Population pharmacokinetics was performed using WinNonMix® (Pharsight, Cary, NC). A one-compartment model was fitted to the data. Health status (presence or absence of babesiosis), packed cell volume (PCV), serum albumin concentrations, mental status (a marker for the severity of illness) and the presence of splenomegaly significantly influenced the population pharmacokinetics model. The PCV lost its significance when these covariates were modelled concurrently, due to its correlation to the health status. In the final model, the volume of distribution (health status and albumin) and K01 (health status) was significantly influenced by covariates.