Prediction of the residue levels of drugs in eggs, using physicochemical properties and their influence on passive diffusion processes

Abstract

Based on a physiologically based pharmacokinetic model, describing the relationship between the plasma concentration of a drug and its deposition into eggs, general transport constants into yolk and albumen were derived, for a number of compounds, using experimental data from literature. Using only generally accepted concepts in passive diffusion theory, these transport constants were used to derive and calibrate general equations, describing the transport into yolk and albumen, in terms of the physicochemical properties of a drug. It is shown that, in theory, it is possible to calculate/predict the transport constants, using the physicochemical parameters: pKa and plasma protein binding. For a number of sulfonamides, the model was used to predict their distribution between egg yolk and albumen; the outcome was compared to data found in literature. Within this dataset, the lipophilic nature of a drug does not seem to play a major role in explaining the distribution ratio of a drug between albumen and yolk.

Physiological parameter values for physiologically based pharmacokinetic models in food‐producing animals. Part II: Chicken and turkey

“…The edible component of the eggs, the albumen and yolk, is different in physiological and chemical properties. Several published PBPK models have incorporated eggs with or without albumen and yolk being two separated compartments (Hekman & Schefferlie, 2011 ; Lautz et al., 2020 ; Schefferlie & Hekman, 2016 ). It was suggested that the inclusion of both yolk and albumen compartments can aid in predictions of residue profiles depending on the physiochemical properties of the drug (Lautz et al., 2020 ; Schefferlie & Hekman, 2016 ).…”

Ionophore coccidiostats – disposition kinetics in laying hens and residues transfer to eggs

“…The residue profiles of administered drugs that appeared in either egg white or egg yolk were often found to be very different ( Kan and Petz, 2000 ; Furusawa, 2001 ; Goetting et al, 2011 ). Several studies have attempted to explain the critical factors that may influence the transfer of residue and model its distribution to either egg yolk or egg white compartment ( Donoghue et al, 1997 ; Donoghue, 2001 , 2005 ; Furusawa, 2001 ; Goetting et al, 2011 ; Hekman and Schefferlie, 2011 ; Schefferlie and Hekman, 2016 ).…”

“…They concluded that physicochemical properties of a molecule alone cannot always be used to predict its pharmacokinetics. Likewise, Schefferlie and Hekman (2016) suggested that lipid solubility alone is not the only chemical factor to influence the transfer rate and distribution of residues between the egg white and yolk compartments. Even when all of the aforementioned physicochemical parameters are taken into account, it is difficult to predict the distribution of residue between the egg white and yolk after exposure since some of the factors that determine the preference of distribution of the residues between the 2 compartments are still to be characterized ( Furusawa, 2001 ; Kan, 2003 ; Donoghue, 2005 ; Schefferlie and Hekman, 2016 ).…”

“…Despite the fact that a significant set of empirical data has been collected on drug transfer to eggs, modeling these processes may pose a great challenge ( Donoghue, 2005 ). Even though the classical pharmacokinetic models and principles are capable of describing the time-dependent course of residues in plasma and tissues, they fail to do so in developing egg compartments ( Schefferlie and Hekman, 2016 ). Indeed, in contrast to drug concentrations in the egg white, its concentrations in egg yolk do not parallel with the concentrations in plasma ( Schefferlie and Hekman, 2016 ).…”

Antimicrobiële resistentie en residuen van diergeneesmiddelen (antibiotica) in een circulaire veehouderij : Tegengaan van verspreiding via mest en milieu

“…Daarom worden eisen gesteld ten aanzien van tijd en residuen voor menselijke consumptie. Daarom zijn zeer weinig diergeneesmiddelen goedgekeurd voor gebruik bij leghennen, en is het aantal geneesmiddelen met een Europese maximumwaarde voor residuen ook erg klein gebleven in de laatste jaren (Schefferlie & Hekman, 2018 een patiënt was met een resistente bacterie tegen carbapenem-antibiotica die in het water van de afvoer van de douche kon groeien en zich via de lucht verspreidde als de douche aanstond (zie ook,…”