Mechanism for transport of ivermectin to the stratum corneum in rats

Ivermectin (IVM) is used as an oral medication for scabies, a skin infection caused by a mite, sarcoptes scabiei, which parasitizes in the stratum corneum. After oral administration IVM is absorbed from the intestine, and finally distributed to the stratum corneum to eliminate the mites. However its transport mechanism remains unclear. A pharmacokinetic study was performed using hairless Wistar Yagi (HWY) rats, which have no or atrophied sebaceous glands, and Wistar rats as a reference. After oral administration of IVM to both groups, the area under the concentration–time curve of IVM in the dermis and epidermis (dermis–epidermis) of HWY rats were about 60% lower than that of Wistar rats, even though the plasma concentration profiles were comparable in both groups. In addition at 12 h after the administration, IVM concentration in the outer stratum corneum, the shallower layer of the dermis–epidermis, was higher compared to that in the deeper layer. In the dermis–epidermis of the skin from various locations, the concentrations of IVM and squalene, the latter of which is secreted to the skin surface via the sebaceous gland, were positively well correlated. Those results suggest that IVM is transported to the stratum corneum via the sebaceous glands.

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