Program

PO2-13-1

POPULATION PHARMACOKINETICS OF GENTAMICIN IN PUPPIES DIAGNOSED WITH PARVOVIRUS ENTERITIS

[Speaker] Fidelis A. Gberindyer:1
[Co-author] Abatan M. Oluwole:2, Shima K. Felix:3, Paolo Denti:4
1:Veterinary Physiology, Pharmacology and Biochemistry, Federal University of Agriculture, Makurdi, Nigeria, 2:Veterinary Pharmacology and Toxicology, University of Ibadan, Ibadan, Nigeria, 3:Gan-Rovet Animal Hospital, Warri, Nigeria, 4:Pharmacometrics Unit, Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, South Africa

Gentamicin is a concentration-dependent antibiotic commonly used in combination with other drugs in managing canine parvovirus enteritis (CPE). Very little is known about the pharmacokinetics of gentamicin in puppies with CPE. The purpose of this study was to evaluate effect of common co-medications, pathophysiologic and other covariates of puppies with CPE on the pharmacokinetics of gentamicin.
Fifty puppies of different breeds such as Alsatian, Rottweiler, Boerboel, Indigenous, and Pit-bull with CPE and median age of 4 months (2-12 months), and body weight (BWT) of 6kg (2-28kg) were administered a single intramuscular dose of gentamicin at 6.0mg/kg. Sparse blood samples were obtained over 24 hours, and serum gentamicin concentrations were quantified with competitive ELISA. Population pharmacokinetics analysis was performed employing non-linear mixed-effect modeling in MONOLIX 4.3.3 to elucidate the effect of breeds, sex, size, age, co-medications, and pathophysiologic covariates on the pharmacokinetics of gentamicin. Simulation of serum concentration-time profiles at different dosing scenarios was performed with MLXPlore 1.1.1.
A two-compartment model with first-order absorption and elimination described the pharmacokinetics of gentamicin. None of the investigated covariates was found to significantly (OFV<3.84) affect gentamicin pharmacokinetics. However, allometric scaling with BWT and estimated exponents was found to account well for the effect of body size on clearance (CL) and volume of distribution (V). Also, large between-subject variability of 86% was observed in V. Simulations with dose levels 4mg/kg to 10mg/kg showed trough serum concentrations within 0.46-1.47ug/mL with the corresponding steady state concentrations of 5.26-13.17ug/mL at 2.6 hours after the second dose.
Weight was the only covariate affecting pharmacokinetics of gentamicin in our cohort of puppies. Our model indicates that safe and effective serum concentrations were attained at dose levels 6 to 9 mg/kg.

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