Pharmacokinetic analysis of cefquinome after intravenous and intramuscular administration in goats with different physiologic states by Nonlinear Mixed-Effect Modelling

HIMELFARB, M.; SERRANO-RODRIGUEZ, J.M.; ZARAZAGA, M.P; LITTERIO, N.J; DE LUCAS-BURNEO, J.J.; PORTA, L.; SAN ANDRES-LARREA, M.I.

Roma

Congreso; Ninth International Conference on Antimicrobial Agents in Veterinary Medicine (AAVM); 2018

Department of Health, Animal Science and Food Safety (VESPA)

The objective of this study was to evaluate the effect of different physiologic states on the pharmacokinetics of cefquinome in adult goats (2 mg/kg), administered by intravenous and intramuscular administration, by nonlinear mixed-effects model. Eighteen healthy adult goats: 6 non-pregnant (NP), 6 pregnant (P) and 6 in the middle of the lactation period (L), were included in the study. The time of gestation in group P was 12.83±1.17 weeks. Milk production of animals in group L was 1.48±0.48 L/day. Cefquinome sulphate (CFQ) was administered IV or IM at a dose of 2 mg/kg, following a cross over design, with a washout period of 10 days. Blood samples were collected at different time points until 48 h for both routes. CFQ quantification in serum samples was determined by high performance liquid chromatography with UV detector (HPLC/uv). Concentration vs time data was analyzed with a nonlinear mixed-effect modelling using Monolix (Lixoft, Batiment D, Antony, France), using the Stochastic Approximation Expectation-Maximization (SAEM) algorithm. A bi-compartmental pharmacokinetic model with a combined and proportional error models were selected for IV and IM routes, respectively. The physiological covariates age, weight, non-pregnant, pregnant and lactating states, were evaluated in order to determine its effect on the estimated pharmacokinetic parameters Ka (absorption constant; only for IM route), Cl (clearance of the central compartment), V1 (volume of distribution of central compartment), Q (inter-compartmental clearance) and V2 (volume of distribution of peripheral compartment). The covariates were included in the model if showed statistical significance (p