Larsen Karen E, Lifschitz Adrián L, Lanusse Carlos E, Virkel Guillermo L
Laboratorio de Ecotoxicología y Biología Celular, Facultad de Ciencias Veterinarias, UNCPBA, Tandil, Argentina.
Laboratorio de Farmacología, Centro de Investigación Veterinaria de Tandil (CIVETAN-CIC-CONICET), Facultad de Ciencias Veterinarias, UNCPBA, Tandil, Argentina.
J Vet Pharmacol Ther. 2019 Sep;42(5):548-555. doi: 10.1111/jvp.12798. Epub 2019 Jul 22.
The combination of the organophosphate (OP) chlorpyrifos (CPF) and the pyrethroid cypermethrin (CPM) is commonly marketed as pour-on formulations for the control of sheep lice, ked, and blowflies. CPF irreversibly inhibits acetylcholinesterases (AChE), while pyrethroids are not AChE inhibitors. However, combinations of pyrethroids with OPs showed a highly synergistic effect on AChE inhibition. Thus, the aim of the current work was to evaluate in vitro and in vivo the inhibitory potency of both pesticides, alone and in combination with AChE and butyrylcholinesterase (BChE) activities in sheep blood. In vitro, IC50 values were similar after CPF or CPF plus CPM incubations. The pour-on coadministration of recommended doses of CPF and CPM did not cause a significant inhibition of AChE and BChE in sheep blood. Only slight percentages of inhibition of their catalytic activities were observed when both drugs were given at 4-fold higher dose rates. The lower systemic availability of topical administration of OPs in sheep may help to explain the lower degree of inhibition of blood AChE and BChE in vivo. The results emerged from this research are a further contribution to the knowledge of the risks of implementing higher dosage regimens of OPs-containing antiparasitic formulations.
有机磷酸酯（OP）毒死蜱（CPF）与拟除虫菊酯氯氰菊酯（CPM）的组合通常以浇泼剂配方销售，用于控制绵羊身上的虱子、蜱蝇和绿蝇。CPF不可逆地抑制乙酰胆碱酯酶（AChE），而拟除虫菊酯不是AChE抑制剂。然而，拟除虫菊酯与OP的组合对AChE抑制表现出高度协同效应。因此，当前工作的目的是在体外和体内评估这两种杀虫剂单独以及与绵羊血液中的AChE和丁酰胆碱酯酶（BChE）活性联合使用时的抑制效力。在体外，CPF或CPF加CPM孵育后的半数抑制浓度（IC50）值相似。按推荐剂量浇泼施用CPF和CPM不会对绵羊血液中的AChE和BChE产生显著抑制。当两种药物以高4倍的剂量率给药时，仅观察到其催化活性有轻微的抑制百分比。绵羊中OP局部给药的全身可用性较低，这可能有助于解释体内血液AChE和BChE的抑制程度较低。这项研究的结果进一步有助于了解实施含OP抗寄生虫制剂更高剂量方案的风险。
