Modeling drug residue uptake by eggs: yolks contain ampicillin residues even after drug withdrawal and nondetectability in the plasma

The present study was conducted to determine whether: 1) preovulatory yolks may be an important storage depot for drug residues in eggs laid days to weeks after drug withdrawal; and 2) the prediction model based on the pattern of drug incorporation in developing yolks is predictive of the pattern of residues contained in the sequence of eggs laid during and after drug withdrawal. To test these possibilities, 24 hens were dosed for either 1, 2, or 3 d with ampicillin, and the content and pattern of residues in laid eggs were evaluated during and after dosing. Hens were bled 24 h after the final dosing, and plasma ampicillin concentrations were determined. Ampicillin was used in this study because it has an extremely short plasma halflife in laying hens that limits additional drug transfer after drug withdrawal. Ampicillin concentrations were not detectable in plasma from hens injected with ampicillin for either 1, 2 or 3 d (assay sensitivity of 0.6 ng/ml or 0.6 ppb). Hens from all three injection groups produced eggs containing detectable ampicillin residues for 6 d after the last injection. These data demonstrate that drug residues are contained in eggs laid a number of days after drug withdrawal. Because plasma ampicillin was not detectable even 24 h after final dosing, the majority, if not all, of the incurred ampicillin residues contained in eggs laid after drug withdrawal were due to incorporation and storage of drug in preovulatory yolks during the dosing period. Additionally, accounting for ampicillin's stability, our model is predictive of the pattern of residues contained in eggs. These data emphasize the importance of transfer and storage of drugs in preovulatory yolks as a significant contributing mechanism for the production of incurred drug residues in eggs.