Lotilaner

Lotilaner is a gamma-aminobutyric acid (GABA)-gated chloride channel inhibitor selective for mites. Inhibition of these GABA chloride channels causes a paralytic action in the target organism leading to its death. Lotilaner is not an inhibitor of mammalian GABA mediated chloride channels when tested at up to 30 µM (18 µg/mL) in vitro (approximately 1100 times the RHOD).

The systemic pharmacokinetic profile after topical ocular administration was evaluated in healthy volunteers after single and repeat dose administration. The systemic exposure was evaluated in patients at the end of 6 weeks of treatment.

Absorption

Maximum lotilaner concentration was observed 2 hours after a single ocular administration on Day 1 and 1 hour after the last drug administration on Day 42. In healthy subjects, the peak concentration (C_max) and total exposure (AUC_0-12) of lotilaner in whole blood increased after 42 days of repeated ocular administration from 0.596 to 17.8 ng/mL and from 5.75 to 149 hr•ng/mL for C_max and AUC_0-12 respectively. The effective half-life of lotilaner, which is based on the accumulation ratio over the dosing interval of 12 hours, was 264 hours (11 days). In patients with Demodex blepharitis (n=138) who received lotilaner twice daily for 42 days, the mean (range) systemic exposure at the end of treatment was 12.0 ng/mL (0.4-46.1 ng/mL).

Distribution

Lotilaner plasma protein binding is high (>99.9%) in human plasma. The partitioning of lotilaner to human blood cells is approximately 10% (range 0-20%).

Elimination

The effective half-life in healthy subjects, which is based on the accumulation ratio over the dosing interval of 12 hours, is 264 hours (11 days).

Metabolism

Lotilaner is not metabolized by CYP enzymes.