Ivermectin as a potential COVID-19 treatment from the pharmacokinetic point of view

Georgi Momekov; Denitsa Momekova

Ivermectin is a semisynthetic analogue of the natural product avermectin B 1a , a lipophilic macrolide isolated from Streptomyces avermitilis developed as a crop management insecticide. Ivermectin affects a plethora of ivertebrate species, incl. parasitic nematodes, arachnids, and insects. Its mode of action on target species is by potentiating GABA-mediated neurotransmission and by binding to glutamategated Clchannels, found only in invertebrates 13 . The drug induces tonic paralysis of the musculature of susceptible parasites, and eventually death 13 . At the recommended doses, ivermectin does not readily penetrate the CNS of mammals, where GABA functions as a neurotransmitter 13, 15 . Conversely in healthy volunteers and infected patients the drug is usually well tolerated at the therapeutic dose ranges [12] [13] [14] . A recent meta-analysis has shown that even larger doses (up to 800 µg/kg) with a several years period of follow-up could be well tolerated in patients with parasitic infections 16 . The largest dose intensity with registered pharmacokinetic parameters in healthy subjects is 120 mg, corresponding to up to 2000 µg/kg 12 .