Pharmacokinetic studies of different drugs in geese

This PhD research is composed by different pharmacokinetic studies and tissue residue analysis performed in geese, an underestimated species that in some countries have been domesticated since long time for the production of meat, eggs, and feathers. One of the main objectives of veterinary pharmacology is preserve food producing animals’ health, preventing potential diseases, increasing the animals’ performances and, on the other hand, to guarantee an adequate amount of food with the lowest economic losses. It is well known that for a good livestock production the use of drugs is necessary. Pharmaceutical companies invest big budgets and efforts to elucidate the pharmacokinetics, pharmacodynamics and safety profile of drugs in major food producing species. Unfortunately, the economic return of these studies is not positive when minor species are accounted. Often even minor species require therapeutic treatments, and since no information is available, doses and potential therapeutic effects are extrapolated by other animals. This dangerous practice can lead to drug ineffectiveness or toxicity and since no MRL and withdrawal time are available residues may be present in the animal’s products intended for human consumption. The goose belongs to the minor species food producing animal class and very little information is present about drugs in this bird. A deep knowledge of the pharmacokinetic characteristics and tissue residue profile of a drug in geese is the starting point of the process that is essential for the rational drug usage, ensuring an efficacious treatment in the goose as well as the consumers’ safety. In order to achieve this target, different drugs belonging to the most important classes of drugs used in veterinary medicine have been studied. Five antimicrobial drugs (marbofloxacin, danofloxacin, levofloxacin, doxycycline, amoxicillin), two painkiller drugs (meloxicam, acetaminophen) and one antiparasitic drug (ivermectin). For each of these drugs an appropriate analytical method has been validated for their quantification according to the European Medicines Agency guideline. The selected drugs, and in some cases their metabolites, have been quantified in different matrices (e.g. plasma, different animal tissues) using high-performance liquid chromatography with ultraviolet or fluorescence detector as well as liquid chromatography - tandem mass spectrometry. The pharmacokinetic parameters have been carried out using a pharmacokinetic software and drug plasma concentration profiles have been provided after different routes of administration. The residues analysis has been performed to describe the accumulation of the drug in the edible tissues and for the calculation of an appropriate withdrawal time, a crucial factor for ensuring food safety. In some cases, an in silico pharmacokinetic simulation has been performed to reproduce the in-field breeding condition. The PK/PD surrogates (when available) have been used to predict if the achieved plasma concentrations might be therapeutic. In addition, under the same attitude to “bring new knowledge in the veterinary pharmacology field” novel drugs have been tested in different animal species and reviews published to facilitate the studies of other colleagues.

This PhD research is composed by different pharmacokinetic studies and tissue residue analysis performed in geese, an underestimated species that in some countries have been domesticated since long time for the production of meat, eggs, and feathers. One of the main objectives of veterinary pharmacology is preserve food producing animals’ health, preventing potential diseases, increasing the animals’ performances and, on the other hand, to guarantee an adequate amount of food with the lowest economic losses. It is well known that for a good livestock production the use of drugs is necessary. Pharmaceutical companies invest big budgets and efforts to elucidate the pharmacokinetics, pharmacodynamics and safety profile of drugs in major food producing species. Unfortunately, the economic return of these studies is not positive when minor species are accounted. Often even minor species require therapeutic treatments, and since no information is available, doses and potential therapeutic effects are extrapolated by other animals. This dangerous practice can lead to drug ineffectiveness or toxicity and since no MRL and withdrawal time are available residues may be present in the animal’s products intended for human consumption. The goose belongs to the minor species food producing animal class and very little information is present about drugs in this bird. A deep knowledge of the pharmacokinetic characteristics and tissue residue profile of a drug in geese is the starting point of the process that is essential for the rational drug usage, ensuring an efficacious treatment in the goose as well as the consumers’ safety. 11 In order to achieve this target, different drugs belonging to the most important classes of drugs used in veterinary medicine have been studied. Five antimicrobial drugs (marbofloxacin, danofloxacin, levofloxacin, doxycycline, amoxicillin), two painkiller drugs (meloxicam, acetaminophen) and one antiparasitic drug (ivermectin). For each of these drugs an appropriate analytical method has been validated for their quantification according to the European Medicines Agency guideline. The selected drugs, and in some cases their metabolites, have been quantified in different matrices (e.g. plasma, different animal tissues) using high-performance liquid chromatography with ultraviolet or fluorescence detector as well as liquid chromatography - tandem mass spectrometry. The pharmacokinetic parameters have been carried out using a pharmacokinetic software and drug plasma concentration profiles have been provided after different routes of administration. The residues analysis has been performed to describe the accumulation of the drug in the edible tissues and for the calculation of an appropriate withdrawal time, a crucial factor for ensuring food safety. In some cases, an in silico pharmacokinetic simulation has been performed to reproduce the in-field breeding condition. The PK/PD surrogates (when available) have been used to predict if the achieved plasma concentrations might be therapeutic. In addition, under the same attitude to “bring new knowledge in the veterinary pharmacology field” novel drugs have been tested in different animal species and reviews published to facilitate the studies of other colleagues.