Physiological parameter values for physiologically based pharmacokinetic models in food‐producing animals. Part I: Cattle and swine

Abstract

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.

Physiological parameter values for physiologically based pharmacokinetic models in food‐producing animals. Part III: Sheep and goat

“…The calculated mean for relative blood weight in sheep is 5.22% in Table 3 , and 4.86% and 5.29% for market‐age sheep and lambs, respectively, which are all comparable to the value of 4.31% in cattle (Lin et al., 2020 ) and close to the values of 5.7% (Upton, 2008 ) and 4.7% (Lautz, Dorne, et al., 2020 ) from previous reviews on sheep. Based on data reported in a previous study for neonatal sheep (Hansard, 1956 ), the average relative weight of the blood in fetal and neonatal sheep is approximately 9.30% of the body weight as shown in Table 6 .…”

“…The mean value for market‐age sheep is 0.006% (Table 4 ) and is 0.008% for lambs (Table 5 ). These values are comparable to the tissue weight of adrenal glands in beef cattle and dairy cows of 0.006% (Lin et al., 2020 ). The value of adrenal glands for fetal sheep is 0.022% (Table 6 ), which is much higher than those in market‐age sheep and lambs.…”

“…The methods on the literature search strategy, literature inclusion/exclusion criteria, data digitalization, standardization, and analysis, as well as the equations used in the calculation are the same as the methods described in detail in Parts I and II of this manuscript series (Lin et al., 2020 ; Wang et al., 2020 ). Readers are referred to these earlier publications for detailed methodology.…”

“…In terms of food animals, our group recently completed a comprehensive review on physiological parameters of body weight, organ/tissue weights, cardiac output, regional blood flow, and hematocrit in different species, including cattle, swine, chickens, turkeys, sheep, and goats. The manuscript describing the compiled data in cattle and swine has been published (Lin et al., 2020 ); the manuscript describing data in chickens and turkeys is under review (Wang et al., 2020 ); the present manuscript is the final part of this series and focuses on sheep and goats. The data are presented in the format of mean and standard deviation ( SD ) so that they can directly be used to characterize the variability of each physiological parameter and to create stochastic population PBPK models.…”

Application of a Physiologically Based Pharmacokinetic Model to Develop a Veterinary Amorphous Enrofloxacin Solid Dispersion

“…The PBPK model in pigs of ENR granules was built with acslXtreme (version 3.0, The Aegis, Technologies Group, Inc. Huntsville, AK, USA). The physiological parameters of pigs and the chemical-specific parameters for ENR in pigs are from the literature [ 37 , 38 , 39 , 40 , 41 ] and are provided in Supplementary Tables S1 and S2 . The model included the oral administration module, gastrointestinal tract, plasma, liver, kidney, fat, muscle, lung, and the rest of the body ( Figure 2 ).…”