Browsing by Author "Lin, Zhoumeng"

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    Comparative Pharmacokinetics and Tissue Concentrations of Flunixin Meglumine and Meloxicam in Tilapia (Oreochromis spp.)
    Martin, Miriam; Smith, Stephen A.; Kleinhenz, Michael; Magnin, Geraldine; Lin, Zhoumeng; Kuhn, David; Montgomery, Shawnee; Coetzee, Johann (MDPI, 2021-11-25)
    Evidence of pain perception in fish is well established, but analgesic use in aquaculture is limited. The objective was to investigate the comparative pharmacokinetics of flunixin administered intramuscularly (IM) and meloxicam administered IM or orally (PO) in tilapia. Two hundred and seventy fish were assigned to 1 of 3 treatment groups: flunixin meglumine IM (2.2 mg/kg); meloxicam IM (1 mg/kg); or meloxicam PO (1 mg/kg). Blood and tissue samples were collected from 6 fish per treatment at 14 time points for 10 days. Drug concentrations were determined using ultra-high-pressure liquid chromatography coupled with mass spectroscopy. Plasma concentration versus time data were analyzed with a non-compartmental approach using a commercially available software. Flunixin reached a mean maximum concentration (Cmax) of 4826.7 ng/mL at 0.5 h, had a terminal half-life (T1/2) of 7.34 h, and an area under the concentration–time curve extrapolated to infinity (AUCINF_obs) of 25,261.62 h·ng/mL. Meloxicam IM had a T1/2 of 9.4 h after reaching a Cmax of 11.3 ng/mL at 2 h, with an AUCINF_obs of 150.31 h·ng/mL. Meloxicam PO had a T1/2 of 1.9 h after reaching a Cmax of 72.2 ng/mL at 2 h, with an AUCINF_obs of 400.83 h·ng/mL. Tissue concentrations of both drugs were undetectable by 9 h. Flunixin reached a sufficient plasma concentration to potentially have an analgesic effect, while meloxicam, when administered at the given dosage, likely would not.
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    An Interactive Generic Physiologically Based Pharmacokinetic (igPBPK) Modeling Platform to Predict Drug Withdrawal Intervals in Cattle and Swine: A Case Study on Flunixin, Florfenicol, and Penicillin G
    Chou, Wei-Chun; Tell, Lisa A.; Baynes, Ronald E.; Davis, Jennifer L.; Maunsell, Fiona P.; Riviere, Jim E.; Lin, Zhoumeng (Oxford University Press, 2022-07-28)
    Violative chemical residues in edible tissues from food-producing animals are of global public health concern. Great efforts have been made to develop physiologically based pharmacokinetic (PBPK) models for estimating withdrawal intervals (WDIs) for extralabel prescribed drugs in food animals. Existing models are insufficient to address the food safety concern as these models are either limited to 1 specific drug or difficult to be used by non-modelers. This study aimed to develop a user-friendly generic PBPK platform that can predict tissue residues and estimate WDIs for multiple drugs including flunixin, florfenicol, and penicillin G in cattle and swine. Mechanism-based in silico methods were used to predict tissue/plasma partition coefficients and the models were calibrated and evaluated with pharmacokinetic data from Food Animal Residue Avoidance Databank (FARAD). Results showed that model predictions were, in general, within a 2-fold factor of experimental data for all 3 drugs in both species. Following extralabel administration and respective U.S. FDA-approved tolerances, predicted WDIs for both cattle and swine were close to or slightly longer than FDA-approved label withdrawal times (eg, predicted 8, 28, and 7 days vs labeled 4, 28, and 4 days for flunixin, florfenicol, and penicillin G in cattle, respectively). The final model was converted to a web-based interactive generic PBPK platform. This PBPK platform serves as a user-friendly quantitative tool for real-time predictions of WDIs for flunixin, florfenicol, and penicillin G following FDA-approved label or extralabel use in both cattle and swine, and provides a basis for extrapolating to other drugs and species.
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    Pharmacokinetic Parameters and Estimating Extra-Label Tissue Withdrawal Intervals Using Three Approaches and Various Matrices for Domestic Laying Chickens Following Meloxicam Administration
    Richards, Emily D.; Dutch, Rachel S.; Burmas, Nathaniel C.; Davis, Jennifer L.; Lin, Zhoumeng; Clapham, Maaike O.; Wetzlich, Scott E.; Tell, Lisa A. (Frontiers, 2022-03-03)
    Meloxicam is commonly prescribed for treating chickens in backyard or small commercial operations despite a paucity of scientific data establishing tissue withdrawal interval recommendations following extra-label drug use (ELDU). Historically, ELDU withdrawal intervals (WDIs) following meloxicam administration to chickens have been based on the time when meloxicam concentrations fall below detectable concentrations in plasma and egg samples. To date, no studies have addressed tissue residues. ELDU WDIs are commonly calculated using terminal elimination half-lives derived from pharmacokinetic studies. This study estimated pharmacokinetic parameters for laying hens following meloxicam administration and compared ELDU WDIs calculated using tissue terminal elimination half-lives vs. those calculated using FDA tolerance and EMA's maximum regulatory limit statistical methods, respectively. In addition, ELDU WDIs were calculated using plasma meloxicam concentrations from live birds to determine if plasma data could be used as a proxy for estimating tissue WDIs. Healthy domestic hens were administered meloxicam at 1 mg/kg intravenous (IV) once, 1 mg/kg orally (PO) once daily for eight doses or 1 mg/kg PO twice daily for 20 doses. Analytical method validation was performed and meloxicam concentrations were quantified using high-performance liquid chromatography. In general, the terminal elimination technique resulted in the longest ELDU WDIs, followed by the FDA tolerance and then EMA's maximum residue limit methods. The longest ELDU WDIs were 72, 96, and 384 (or 120 excluding fat) h for the IV, PO once daily for eight doses, and PO twice daily for 20 doses, respectively. Plasma data are a possible dataset for estimating a baseline for tissue ELDU WDI estimations when tissue data are not available for chickens treated with meloxicam. Finally, pharmacokinetic parameters were similar in laying hens to those published for other avian species.
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    Physiological parameter values for physiologically based pharmacokinetic models in food-producing animals. Part I: Cattle and swine
    Lin, Zhoumeng; Li, Miao; Wang, Yu-Shin; Tell, Lisa A.; Baynes, Ronald E.; Davis, Jennifer L.; Vickroy, Thomas W.; Riviere, Jim E. (Wiley, 2020-04-08)
    Physiologically based pharmacokinetic (PBPK) models for chemicals in food animals are a useful tool in estimating chemical tissue residues and withdrawal intervals. Physiological parameters such as organ weights and blood flows are an important component of a PBPK model. The objective of this study was to compile PBPK-related physiological parameter data in food animals, including cattle and swine. Comprehensive literature searches were performed in PubMed, Google Scholar, ScienceDirect, and ProQuest. Relevant literature was reviewed and tables of relevant parameters such as relative organ weights (% of body weight) and relative blood flows (% of cardiac output) were compiled for different production classes of cattle and swine. The mean and standard deviation of each parameter were calculated to characterize their variability and uncertainty and to allow investigators to conduct population PBPK analysis via Monte Carlo simulations. Regression equations using weight or age were created for parameters having sufficient data. These compiled data provide a comprehensive physiological parameter database for developing PBPK models of chemicals in cattle and swine to support animal-derived food safety assessment. This work also provides a basis to compile data in other food animal species, including goats, sheep, chickens, and turkeys.