Veterinary pharmacovigilance. Part 6. Predictability of adverse reactions in animals from laboratory toxicology studies

Abstract

Toxicological studies are conducted on constituents of veterinary medicinal products for a number of reasons. Aside from being a requirement of legislation, they are carried out for predictive purposes in the assessment of user safety or for the determination of consumer safety, for example, in the elaboration of maximum residue limits or tolerances. Alternatively, the results of toxicology studies may be available as they have been generated for registration of the drug for human medicinal purposes. This paper examines if the results of such studies have any predictive value for adverse reactions, which might occur during clinical use in animals. A number of adverse reactions, notably the Type A (toxicology or pharmacology dependent) should be predictable from these laboratory studies. However, as with human pharmaceutical products, they have less utility in predicting Type-B reactions (idiosyncratic in nature).

Nervous System and Special Sense Organs

“…As in other neural tissues this is characterized by necrosis of white and gray matter, reactive astrocytosis and vascular endothelial proliferation and fibrinoid necrosis. 403 Similar findings have not been reported in other animal species or with other closely related fluoroquinolones used widely in humans. Although generally well tolerated, high doses of enrofloxacin are reported to induce retinal damage in cats.…”

Investigation of pharmacokinetic interaction between ivermectin and praziquantel after oral administration in healthy dogs

“…The drug is exceptionally safe for mammalians. However, adverse effects observed in some dog and cattle breeds (Collie and Australian shepherd dogs, Murray Grey cattle) are related to neuro‐intoxication with GABA receptor stimulation, which was due to deficient of P‐glycoprotein (P‐gp) (Woodward, ). The first defense against orally ingested toxins and xenobiotics is the gastrointestinal tract which contains cells that express high levels of P‐gp, and P‐gp plays a critical role in pharmacokinetics and toxicokinetics (Chan, Lowes, & Hirst, ; Szakacs, Varadi, Ozvegy‐Laczka, & Sarkadi, ).…”

An easy and green assay to determine albendazole and ivermectin in veterinary preparations by micellar liquid chromatography

“…Albendazole (ALB), a benzimidazole, and ivermectin (IVE), a macrocyclic lactone, are well-tolerated broadspectrum veterinary anthelminthic agents [4,5]. Therapies based on ALB + IVE enhance clinical effects compared to ALB or IVE alone [6].…”