Lotilaner

Absorption

Tmax is about two hours after a single ocular administration on Day 1 and one hour after the last drug administration on Day 42. In healthy subjects, the peak concentration (Cmax) in whole blood increased after 42 days of repeated ocular administration, from 0.596 to 17.8 ng/mL. The total exposure (AUC0-12) also increased from 5.75 to 149 hr x ng/mL.
In patients with Demodex blepharitis who received lotilaner twice daily for 42 days, the mean systemic exposure at the end of treatment was 12.0 ng/mL, with a range of 0.4-46.1 ng/mL.

Toxicity

There is no information available regarding the overdosage and acute toxicity of lotilaner.

Description

Lotilaner is a representative of the isoxazolines, a new class of insecticides discovered in the 2000s.
Isoxazolines (Afoxolaner, Fluralaner, Lotilaner, and Sarolaner) Isoxazolines are insecticidal and arachnicidal substances that can be given orally, or topically as spot-ons, and act systemically in the blood circulation.
lotilaner (Credeliot), a novel oral isoxazoline against naturally occurring mange mite infestations in dogs caused by Demodex spp.
Lotilaner, like the other isooxazolines is active against fleas, mites, and ticks. After oral administration or topical application, it can kill fleas rapidly.

The Uses of Lotilaner

Lotilaner is a new member of the isoxazoline class for the treatment of flea and tick infestations in cats.

Indications

Lotilaner is indicated for the treatment of Demodex blepharitis.

Background

Lotilaner is an ectoparasiticide that is a member of the isoxazoline family of compounds. Lotilaner has largely been used for veterinary uses as an antiparasitic agent to treat flea and tick infestations in animals. Lotilaner consists of two enantiomers: the S-enantiomer is active in vivo, while the R-enantiomer is reported to exhibit low biological activity. The active ingredient found in drug products of lotilaner is the S-enantiomer.
On July 25, 2023, lotilaner was approved by the FDA for the treatment of Demodex blepharitis, making it the first and only approved therapeutic for this condition.

Indications

Lotilaner is a monthly chewable tablet for the treatment and prevention of fleas and ticks. It is used in dogs and puppies 8 weeks of age or older weighing 4.4 pounds or greater (Elanco, 2019).

Pharmacokinetics

Lotilaner is a parasiticide that works against Demodex mites that cause Demodex blepharitis. It is also active against insects, ticks, and lice. Its activity is arthropod-specific, as it does not bind to the same therapeutic target in mammals.

Side Effects

These include weight loss, elevated blood urea nitrogen, increased urination, and diarrhea (Elanco, 2019).

Metabolism

In cats, mininal metabolism of lotilaner was observed. Lotilaner is not metabolized by CYP enzymes.

Mode of action

Lotilaner is available for oral administration to dogs (CREDELIO), i.e. it has a systemic mode of action. Ingested lotilaner is rapidly absorbed into blood and distributed throughout the whole body of the treated dog. Blood-sucking parasites (mainly fleas and ticks) are killed during their blood meal.
But the systemic mode of action means also that for fleas and/or ticks to be killed, they have to bite the dog first and suck enough blood before the ingested active ingredient kills them.
As other isoxazolines with insecticidal and tickicidal efficacy, lotilaner is a non-competitive GABA (gamma-aminobutyric acid) receptor antagonist, much more selective for GABA receptors in insects or ticks, than for those in mammals, including humans. It binds to chloride channels in nerve and muscle cells, which blocks the transmission of neuronal signals. Affected parasites are paralyzed and die.