Detoxification of ivermectin by ATP binding cassette transporter C4 and cytochrome P450 monooxygenase 6CJ1 in the human body louse, Pediculus humanus humanus

A new study investigating the functional properties of ivermectin-induced detoxification genes suggests that ATP binding cassette transporter C4 (PhABCC4) and cytochrome P450 6CJ1 (CYP6CJ1) are involved in the Phase III and Phase I xenobiotic metabolism of ivermectin respectively.

The study by Kim et.al published in the September 2017 Journal of Insect Molecular Biology investigated the functional properties of PhABCC4 and CYP6CJ1 after expression in either X. laevis oocytes or using a baculovirus expression system, respectively.

Efflux of ([3 H]-PMEA), a known ABCC4 substrate in humans, was detected from PhABCC4 cRNA-injected oocytes by liquid scintillation spectrophotometric analysis and PhABCC4 expression in oocytes was confirmed using ABC transporter inhibitors. Using a variety of insecticides in a competition assay, only co-injection of ivermectin and dichlorodiphenyltrichloroethane led to decreased efflux of [3 H]-PMEA. PhABCC4-expressing oocytes also directly effluxed [3 H]-ivermectin, which increased over time.

The findings also revealed that ivermectin appeared to be oxidatively metabolized and/or sequestered, although at low levels, following functional expression of CYP6CJ1 along with cytochrome P450 reductase in Sf9 cells.