The objective of this study was to develop a nonlinear mixed‐effects model of vitacoxib disposition kinetics in dogs after intravenous (I.V.), oral (P.O.), and subcutaneous (S.C.) dosing. Data were pooled from four consecutive pharmacokinetic studies in which vitacoxib was administered in various dosing regimens to 14 healthy beagle dogs. Plasma concentration versus time data were fitted simultaneously using the stochastic approximation expectation maximization (SAEM) algorithm for nonlinear mixed‐effects as implemented in Monolix version 2018R2. Correlations between random effects and significance of covariates on population parameter estimates were evaluated using multiple samples from the posterior distribution of the random effects. A two‐compartment mamillary model with first‐order elimination and first‐order absorption after P.O. and S.C. administration, best described the available pharmacokinetic data. Final parameter estimates indicate that vitacoxib has a low‐to‐moderate systemic clearance (0.35 L hr−1 kg−1) associated with a low global extraction ratio, but a large volume of distribution (6.43 L/kg). The absolute bioavailability after P.O. and S.C. administration was estimated at 10.5% (fasted) and 54.6%, respectively. Food intake was found to increase vitacoxib oral bioavailability by a fivefold, while bodyweight (BW) had a significant impact on systemic clearance, thereby confirming the need for BW adjustment with vitacoxib dosing in dogs.

Typhoid fever is a devastating disease that kills more than 115,000 people every year and is caused by Salmonella Typhi. Typhoid toxin, exclusively produced by S .

Ceftiofur (CEF) sodium is a third-generation broad-spectrum cephalosporin commonly used in an extra-label manner in dogs for the treatment of respiratory and urinary system infections. To contribute to the literature supporting CEF use in companion animals, we have developed a compartmental, non-linear mixed-effects (NLME) model of CEF pharmacokinetics in dogs (PK). We then used the mathematical model to predict (via Monte Carlo simulation) the duration of time for which plasma concentrations of CEF and its pharmacologically active metabolites remained above minimum inhibitory concentrations (respiratory tract Escherichia coli spp.). Twelve healthy beagle dogs were administered either 2.2 mg/kg ceftiofur-sodium (CEF-Na) intravenously (I.V) or 2.2 mg/kg CEF-Na subcutaneously (S.C). Plasma samples were collected over a period of 72 h post-administration. To produce a measurement of total CEF, both CEF and CEF metabolites were derivatized into desfuroylceftiofur acetamide (DCA) before analysis by UPLC-MS/MS. No adverse effects were reported after I.V or S.C dosing. The NLME PK models were parameterized using the stochastic approximation expectation maximization algorithm as implemented in Monolix 2018R2. A two-compartment mamillary model with first-order elimination and first-order S.C absorption best described the available kinetic data. Final parameter estimates indicate that CEF has a low systemic clearance (0.25 L/h/kg) associated with a low global extraction ratio E = 0.02) and a moderate volume of distribution (2.97 L/kg) in dogs. The absolute bioavailability after S.C administration was high (93.7%). Gender was determined to be a significant covariate in explaining the variability of S.C absorption. Our simulations predicted that a dose of 2.2 mg/kg CEF-Na S.C would produce median plasma concentrations of CEF of at least 0.5 μg/mL (MIC50) for ~30 h.

The aminoglycoside antibiotic neomycin, which is used to treat external or internal bacterial infections, is primarily administered in veterinary medicine as a sulfate salt. However, no information is available on the pharmacokinetic characteristics and absolute availability of neomycin sulfate after intravenous (i.v.) and oral (p.o.) administrations in swine. Here, these parameters were studied in swine after i.v. and p.o. doses of single 15 mg/kg body weight doses. The blood samples were assessed using ultra‐high‐performance liquid chromatography‐tandem mass/mass spectrometry (UPLC‐MS/MS) and pharmacokinetic parameters were analyzed using a non‐compartmental model. In swine, after the p.o. administration, the elimination half‐life, mean residue time from t0 to the last collection point, mean maximum concentration, mean time to reach maximum concentration and area under concentration–time curve from t0 to the last collection point values were 12.43 ± 7.63 h, 10.25 ± 4.32 h, 0.11 ± 0.07 μg/ml, 1.92 ± 0.97 h and 1.23 ± 0.78 μg·h/ml, respectively, whereas after the i.v. administration, the values were 5.87 ± 1.12 h, 6.07 ± 0.49 h, 15.80 ± 1.32 μg/ml, 0.30 ± 0.38 h and 76.14 ± 3.52 μg·h/ml, respectively. The absolute bioavailability of neomycin sulfate B was 4.84%±0.03.