Neonicotinoid insecticides are used for agricultural and non-agricultural purposes worldwide. Pets are directly exposed to neonicotinoids in veterinary products and through environmental contamination. Cytochrome P450 (CYP) is among the most significant xenobiotic metabolizing enzymes that oxidizes several chemicals, including neonicotinoids. However, CYP activities and metabolite compositions of neonicotinoid metabolites are unknown in most domesticated pet species. Our objectives were to reveal the differences in metabolites of neonicotinoids (imidacloprid, clothianidin, and acetamiprid) and CYP activities among common pet species (cats and dogs), humans, and rats. The results indicated that the CYP-mediated neonicotinoid metabolism was different depending on species and each neonicotinoid. Among these four species, the kinetics of imidacloprid metabolism indicated that rats have the highest rate of oxidation of imidacloprid to 4OH-imidacloprid, while the greatest enzyme kinetics of imidacloprid metabolism to 5OH-imidacloprid were found in rats and humans. Clothianidin was rapidly metabolized to 1-methyl-3-nitroguanidine and dm-clothianidin in rats, but cats and humans showed the lowest formation of dm-clothianidin. CYP activities in metabolism of acetamiprid to dm-acetamiprid and N-acetyl-acetamiprid were determined to be significantly higher in humans compared to other species. However, further studies should be targeted at identifying the differences in hepatic metabolism of neonicotinoids in these species using recombinant CYP enzymes.

新烟碱类杀虫剂在全球范围内用于农业和非农业用途。宠物会直接接触兽药中的新烟碱类物质，并会受到环境污染。细胞色素P450（CYP）是最重要的异源生物代谢酶，可氧化多种化学物质，包括新烟碱类。但是，在大多数驯养宠物物种中，新烟碱类代谢物的CYP活性和代谢物组成均未知。我们的目的是揭示常见宠物（猫和狗），人和大鼠中新烟碱类（吡虫啉，可比丁和乙酰胺）和CYP活性的差异。结果表明，CYP介导的新烟碱代谢因物种和每种新烟碱而不同。在这四个物种中，吡虫啉代谢动力学表明，大鼠和人体内吡虫啉氧化成4OH-吡虫啉的速率最高，而吡虫啉代谢成5OH-吡虫啉的酶动力学最大。在大鼠中，衣藻苷被迅速代谢为1-甲基-3-硝基胍和dm-clothianidin，但猫和人的dm-clothianidin形成最少。CYP在乙酰胺代谢为dm-乙酰胺和经测定，与其他物种相比，人类的N-乙酰基乙酰胺含量显着更高。但是，应使用重组CYP酶进行进一步研究，以鉴定这些物种中新烟碱类药物在肝代谢方面的差异。