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.
