@article{yang_lin_riviere_baynes_2019, title={Development and application of a population physiologically based pharmacokinetic model for florfenicol and its metabolite florfenicol amine in cattle}, volume={126}, ISSN={["1873-6351"]}, DOI={10.1016/j.fct.2019.02.029}, abstractNote={Florfenicol (FF) is used in cattle to treat respiratory diseases but could result in tissue residues. This study aimed to develop a population physiologically based pharmacokinetic (PBPK) model to predict the concentrations of FF and its metabolite, florfenicol amine (FFA), in cattle after four different routes of administration, and to calculate and compare the withdrawal intervals (WDIs) with approved withdrawal times based on different marker residues and their MRLs or tolerances. A flow-limited PBPK model including both FF and FFA sub-models were developed with published data using acslXtreme. This model predicted FF and FFA concentrations in tissues and plasma/serum after intramuscular or subcutaneous administration. Based on the model, the WDIs of 46 and 58 days were calculated to ensure that total residue concentrations (FF + FFA) in 95th percentile of the population after intramuscular and subcutaneous administration were below the MRL, respectively. WDIs were calculated as 44 and 47 days to ensure that FFA concentrations after intramuscular and subcutaneous administration fell below tolerances in 99th percentile of the population, respectively. WDIs were longer than the corresponding label in China, US, and EU. This model provides a useful tool to predict tissue residues of FF and FFA in cattle to improve food safety.}, journal={FOOD AND CHEMICAL TOXICOLOGY}, author={Yang, Fan and Lin, Zhoumeng and Riviere, Jim E. and Baynes, Ronald E.}, year={2019}, month={Apr}, pages={285–294} } @article{yang_yang_yang_kong_wang_bai_2018, title={Pharmacokinetics of minocycline in crucian carp (Carassius auratus) after intravenous and oral administration}, volume={49}, ISSN={["1365-2109"]}, DOI={10.1111/are.13739}, abstractNote={The pharmacokinetic of minocycline was studied after a single intravenous as well as oral dose (5 mg/kg body weight) in crucian carp (Carassius auratus) reared in freshwater at 10°C. Plasma samples were randomly collected from six fish at each sampling time. Plasma concentrations were determined by high‐performance liquid chromatography and further subjected to noncompartmental analysis. Initial concentration of minocycline just after intravenous administration was calculated as 7.320 μg/ml, while the other parameters after intravenous injection were determined as flows: apparent elimination rate constant (λz) of 0.064 per hr, apparent elimination half‐life (t1/2λz) of 10.82 hr, total body clearance (Cl) of 142.72 ml/hr/kg, volume of distribution (Vz) of 2,227.38 ml/kg and volume of distribution at steady‐state (Vss) of 1,937.08 ml/kg. While after oral administration, the λz, t1/2λz, mean absorption time (MAT), absorption half‐life (t₁/₂ₖₐ) and bioavailability were determined as 0.059 per hr, 11.74, 5.55, 3.84 hr, and 81.98%, respectively, and the peak concentration was observed as 1.474 ± 0.362 μg/ml at 8 hr. It was shown that minocycline was slowly but relatively completely absorbed, extensively distributed, and slowly eliminated in crucian carp. Based on the ratios of AUC₀–₂₄ ₕᵣ/MIC90, a minocycline dosage of 5 mg/kg body weight administered intravenously or orally would be only effective to successfully treat crucian carp infected by bacterium with MIC values ≤0.25 μg/ml.}, number={8}, journal={AQUACULTURE RESEARCH}, author={Yang, Fan and Yang, Fang and Yang, Yurong and Kong, Tao and Wang, Guoyong and Bai, Dongying}, year={2018}, month={Aug}, pages={2782–2787} } @article{yang_yang_wang_shi_kong_yang_bai_zhou_2018, title={Pharmacokinetics of orbifloxacin in crucian carp (Carassius auratus) after intravenous and intramuscular administration}, volume={41}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12495}, abstractNote={The pharmacokinetics of orbifloxacin was studied after a single dose (7.5 mg/kg) of intravenous or intramuscular administration to crucian carp (Carassius auratus) reared in freshwater at 25°C. Plasma samples were collected from six fish per sampling point. Orbifloxacin concentrations were determined by high‐performance liquid chromatography with a 0.02 μg/ml limit of detection, then were subjected to noncompartmental analysis. After intravenous injection, initial concentration of 5.83 μg/ml, apparent elimination rate constant (λz) of 0.039 hr−1, apparent elimination half‐life (T1/2λz) of 17.90 hr, systemic total body clearance (Cl) of 75.47 ml hr−1 kg−1, volume of distribution (Vz) of 1,948.76 ml/kg, and volume of distribution at steady‐state (Vss) of 1,863.97 ml/kg were determined, respectively. While after intramuscular administration, the λz, T1/2λz, mean absorption time (MAT), absorption half‐life (T1/2ka), and bioavailability were determined as 0.027 hr−1, 25.69, 10.26, 7.11 hr, and 96.46%, respectively, while the peak concentration was observed as 3.11 ± 0.06 μg/ml at 2.0 hr. It was shown that orbifloxacin was completely but relatively slowly absorbed, extensively distributed, and slowly eliminated in crucian carp, and an orbifloxacin dosage of 10 mg/kg administered intravenously or intramuscularly would be expected to successfully treat crucian carp infected by strains with MIC values ≤0.5 μg/ml.}, number={4}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Yang, F. and Yang, F. and Wang, G. and Shi, W. and Kong, T. and Yang, P. and Bai, D. and Zhou, B.}, year={2018}, month={Aug}, pages={599–604} }