Constantin Roman 1 *, Lavinia Ciucă 2, Andrei Szilagyi 1, 3, Maria-Raluca Gogu 1, 3, Camelia Dascălu 1, 5, Georgiana-Ionela Gotcu 1, Agnes-Iacinta Bacușcă 4, Gabriela-Dumitrița Stanciu 1, Bogdan-Ionel Tamba 1, 5
1 Prof. Ostin C. Mungiu Advanced Research and Development Center for Experimental Medicine – CEMEX, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania
2 Department of Veterinary Medicine and Animal Production, Center for Monitoring of Parasitosis (CREMOPAR), University of Naples Federico II, Naples, Italy
3 Department of Biology, Faculty of Biology, Alexandru Ioan Cuza University of Iasi, Iasi, Romania
4 Department of Family Medicine, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania
5 Department of Pharmacology, Clinical Pharmacology and Algesiology, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania
* Correspondence to: Constantin Roman, Prof. Ostin C. Advanced Research and Development Center for Experimental Medicine (CEMEX), Grigore T. Popa University of Medicine and Pharmacy, University Street No. 16, 700115 Iasi, Romania. E-mail: roman.constantin@umfiasi.ro
Abstract
The aims of this study are to synthesize current evidence on the pathophysiology and clinical spectrum of human demodicosis and to evaluate, from a translational and One Health perspective, the therapeutic potential of isoxazolines—originally developed as veterinary ectoparasiticides—for human Demodex‑associated disease. A narrative review was conducted of clinical and experimental literature on: (i) mechanisms and manifestations of human demodicosis (ocular and cutaneous); (ii) pharmacology, efficacy and safety of isoxazolines (afoxolaner, fluralaner, sarolaner, lotilaner) in canine and feline demodicosis; and (iii) preclinical and clinical data on 0.25% lotilaner ophthalmic solution for Demodex blepharitis. Priority was given to randomized trials, systematic reviews, consensus guidelines and pharmacokinetic/pharmacodynamic studies. Demodex folliculorum and D. brevis are now recognized as density‑dependent drivers of a spectrum of ocular (blepharitis, meibomian gland dysfunction) and cutaneous (rosacea‑like, periorificial, seborrheic‑like) disorders. Current human therapies (systemic tetracyclines and metronidazole, systemic/topical ivermectin, permethrin, tea tree oil and other plant‑derived regimens) provide partial and inconsistent mite control, remain off‑label, and often require chronic use. In contrast, veterinary data show that systemic isoxazolines routinely achieve rapid and sustained >98–99% Demodex reduction in generalized demodicosis, with acceptable safety margins. Translationally, 0.25% lotilaner ophthalmic solution—approved by the FDA in 2023—is the first targeted human therapy for Demodex blepharitis, yielding high rates of collarette resolution and mite eradication after a finite 6‑week course, with minimal systemic exposure and a favourable tolerability profile. Lotilaner’s long half‑life, high protein binding and limited activity on mammalian GABA receptors further support its suitability as a lead candidate. Isoxazolines, particularly lotilaner, show strong promise as targeted therapies for human demodicosis. Building on robust veterinary experience and successful ophthalmic use, carefully designed toxicology, pharmacokinetic and clinical studies are now warranted to develop topical dermal and/or systemic formulations for cutaneous disease and to address outstanding regulatory and safety questions.