Study from Kansas State University's Institute of Computational Comparative Medicine challenges traditional 1xbet best casino website safety assessment method
Tuesday, June 28, 2016
A schematic of a general physiologically based pharmacokinetic — or PBPK — model for the 1xbet best casino website ceftiofur, enrofloxacin, flunixin and sulfamethazine in cattle and swine.| Download 1xbet best casino website photo.
MANHATTAN —Research by 1xbet best casino website 's Institute of Computational Comparative 1xbet best casino website is challenging conventional thought regarding human 1xbet best casino website safety and drug residues found in cattle and swine tissues.
In the 1xbet best casino website "Human 1xbet best casino website Safety Implications of Variation in 1xbet best casino website Animal Drug Metabolism" published recently in Nature's Scientific Reports, Kansas State University researchers Zhoumeng Lin, Christopher Vahl and Jim Riviere found that diseases can dramatically influence the type of drug residue found in tissues of 1xbet best casino website animals that are tested by regulatory agencies in monitoring human 1xbet best casino website safety.
Withdrawal times — the time from last drug administration to slaughter — are determined in healthy animals during the drug development process assuming that the ratio of the marker residue to the total residue produced is constant. This "marker residue ratio" is then used to set legal tissue tolerances in 1xbet best casino website safety inspection programs, but diseases in treated animals may alter this ratio, said Lin, an assistant professor of anatomy and physiology.
"We created a general physiologically based pharmacokinetic — or PBPK — model for representative drugs such as ceftiofur, enrofloxacin, flunixin and sulfamethazine, which are typically used in cattle and swine and have had 1xbet best casino website violations reported," Lin said. "Our simulation results showed that the ratios of the marker residues to the total residues for studied drugs were not fixed values, but time-dependent. Disease changes the ratios substantially, and the degree of change depends on the type of drug, exposure time, tissue and species."
Although it is just one study, the researchers believe their work could have significant impact on 1xbet best casino website safety in the future, said Riviere, director of the Institute of Computational Comparative Medicine. Riviere also is a university distinguished professor, Kansas Bioscience eminent scholar, the MacDonald chair in the College of Veterinary Medicine, and an elected member of the National Academy of Medicine.
"The cornerstone of regulatory chemical 1xbet best casino website safety programs is the monitoring of 1xbet best casino website products for violative chemical residues," Riviere said. "For edible products from 1xbet best casino website -producing animals, such as meat, milk or eggs, residue concentrations are determined based on jurisdictional-specific regulations that result in the determination of a tolerance or maximum residue level for specific drugs in a specific tissue for specific animal species."
The researchers' model was calibrated for each 1xbet best casino website in each species with multiple datasets from the 1xbet best casino website Animal Residue Avoidance Databank, which has an office at 1xbet best casino website .
"We based our results on regression analyses between model-simulated and measured plasma and tissue concentrations of parent drugs and/or major metabolites for each 1xbet best casino website in each species," Lin said. "In general, disease changed the ratios of ceftiofur, enrofloxacin, flunixin and sulfamethazine by several fold, and the ratio could be different by up to several orders of magnitude at the withdrawal time compared to that at the time right after 1xbet best casino website administration."
The results raise a question about the reasonableness of the underlying assumption of using a fixed ratio by the 1xbet best casino website and Drug Administration to determine withdrawal times of veterinary drugs in 1xbet best casino website animals, Riviere said. But he also said the FDA's method is very conservative and safe, and that further study could help provide more accurate data in the future.
Study co-author Vahl is an assistant professor of statistics in the 1xbet best casino website 's College of Arts & Sciences.
The research was supported by the U.S. Department of Agriculture for the 1xbet best casino website Animal Residue Avoidance and Depletion Program, USDA 2013-41480-21001, and the Kansas Bioscience Authority. The idea and need for this analysis originated from a review by Riviere on the USDA's 1xbet best casino website Safety and Inspection Service's National Residue Program conducted for The Pew Charitable Trusts.
