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Credelio lotilaner, whose active pharmaceutical ingredient is lotilaner and Credelio serves as its official commercial trade name, is an innovative oral parasitic insecticide originally researched and launched by Eli Lilly and Company in 2017, specially designed to achieve fast-acting therapeutic intervention against flea and tick infestations in canine pets. Its full systematic chemical name is 5-[5-(3,4,5-trichlorophenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophene-2-carboxylic acid-[2,2,2-trifluoroethyl-aminoformyl)-methyl]-amide. Lotilaner functions as a potent non-competitive antagonist targeting the insect GABA chloride ion channel receptor.
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In in vitro tests, its IC50 value against Drosophila gamma-aminobutyric acid receptors reaches 23.84 nM, while it exerts negligible inhibitory influence on canine endogenous gamma-aminobutyric acid type A receptors, showing outstanding selective safety for host animals. This active ingredient can rapidly clear multiple common canine ectoparasites including fleas as well as brown dog ticks.
As a representative drug of isoxazoline insecticides, since its first application in the field of pet deworming in 2017, Lopinal has rapidly become a core drug for global pet parasite prevention and control due to its unique mechanism of action and broad-spectrum activity. It achieves rapid killing by targeting the parasitic nervous system, combined with the synergistic effect of compound preparations, providing comprehensive protection for pets from external parasites to internal parasites. The specific uses of credelio lotilaner in pet healthcare are systematically explained from four dimensions: prevention and control of pet external parasites, prevention of internal parasites, expansion of special indications, and innovative drug applications.
Pet Parasite Prevention and Control: The Double Killer of Fleas and Ticks
1.1 Rapid eradication of flea infections
Lotelana has a significant killing effect on adult fleas, and its mechanism of action selectively inhibits gamma aminobutyric acid (GABA) gated chloride ion channels in the flea nervous system, leading to neuronal overexcitation and causing paralysis and death. Clinical studies have shown that:Quick acting: The flea killing rate exceeds 99% within 8 hours after administration and reaches 100% within 24 hours.
Blocking the life cycle: By inhibiting the development of eggs and larvae, the flea breeding chain is severed.
Field research in the United States has confirmed that after continuous use for 3 months, the number of fleas in the home environment decreases by 99.5% -100%, and pet skin symptoms significantly improve.Prevention and control of zoonosis risk: fleas can spread pathogens such as cat scratch disease and pestis bacillus. Lotilana reduces the risk of human infection by quickly killing fleas.
1.2 Broad spectrum prevention and control of tick infections
Lotelana has a potent killing effect on high-risk vectors such as tick species and tick species, covering vectors such as solitary tick and brown dog tick that transmit Lyme disease, Babesiosis, and Erich disease.
Broad spectrum activity: Laboratory studies have shown that it has a killing rate of over 97% against ticks such as Tetranychus, Tetranychus, Tetranychus, and Tetranychus within 48 hours after administration.Rapid efficacy: Ticks will be killed 4 hours after administration, with a killing rate of ≥ 97% within 48 hours.Disease prevention: By blocking tick bites, the risk of tick borne diseases such as Lyme disease (transmitted by black legged ticks) can be reduced. The CAPC (Companion Animal Parasitic Committee) in the United States recommends pet owners to use products containing lotilana to prevent the spread of pathogens.
1.3 Efficiency Enhancement of Compound Preparations
Taking Credelio Quattro (compound chewable tablets of Lopina/Moxibustion/Praziquantel/Thiamethoxam) as an example, it enhances the control effect of external parasites through multi-target action:Lothilana: Quickly kills adult fleas and ticks.Moxibustin: Kills surface parasites by opening GABA channels and forms a dual blockade with Lopina.Clinical advantage: Laboratory comparison shows that Credelio Quattro kills ticks twice as quickly as Simparica TRIO (Sarorana/Moxitidine/Thiamethoxam) and NexGard (Afurana).
Prevention of Endoparasites: A Comprehensive Shield between Heartworm and Intestinal Parasites
Prevention of Lymphatic Filariasis
Heartworm disease is caused by canine filariasis and can lead to heart failure in pets. Mosquito bites can infect pets and potentially spread to humans. Lotelana achieves efficient prevention through compound formulations:The function of moxifloxacin: As a macrolide drug, moxifloxacin causes muscle paralysis and death in heartworm larvae by opening glutamate gated chloride ion channels.Clinical data: Laboratory studies have shown that 100% prevention of filariasis can be achieved from the first administration.Safety: Credelio Quattro has good tolerance to dogs infected with adult canine heartworms at maximum recommended doses of 1 and 3.
Treatment of intestinal parasites
Lotelana compound preparation has a potent killing effect on common intestinal parasites such as roundworms, hookworms, and tapeworms:Praziquantel: destroys the tapeworm cortex, induces sustained muscle contraction, and leads to death.Thiamethoxam: As a neuromuscular blocker, it causes paralysis in roundworms and hookworms.Clinical efficacy: The killing rate of roundworm, lion roundworm, and narrow head hook nematode is ≥ 97%, and the cure rate of tapeworm and tapeworm is significant.
Medication regimen and compliance
Usage and Dosage: Credelio Quattro is a beef flavored, non allergenic chewable tablet available in five sizes, with a minimum dose of 20mg/kg lotilana, 0.02mg/kg moxifloxacin, 5mg/kg praziquantel, and 5mg/kg thiazide.Administration method: Must be taken with meals or within 30 minutes after eating, with reduced bioavailability on an empty stomach.Compliance advantage: Administer medication once a month, combined with chewable tablet design, to improve pet owners' medication compliance.
Treatment of Demodex Blepharitis
Credelio lotilaner eye drops (Xdemvy, 0.25%) were approved by the FDA in July 2023, becoming the first treatment drug to directly target the root cause of demodex blepharitis:Mechanism of action: By selectively inhibiting the GABA Cl channel in the body of Demodex mites, the parasite is paralyzed and killed.Clinical study: Two key studies enrolled more than 800 patients, and the results showed that the eradication rate of demodex infection was statistically significant (p<0.001), and the cure rate of eyelid sleeve secretion showed a positive trend (p=0.15).
Market prospects: Yuanda Pharmaceutical plans to officially introduce this veterinary parasiticide product into domestic market in 2024, and its Phase 2 clinical trial targeting meibomian gland dysfunction triggered by ocular Demodex mites is currently steadily underway.
Potential Applications of Lyme Disease Prevention: TP-05, a novel oral lotilaner preparation, is actively undergoing human clinical trials for Lyme disease prevention; this oral formulation effectively lowers infection risk by eliminating pathogenic spirochete bacteria before tick-borne pathogen transmission occurs.
Drug development process and indications
Lotelana was originally developed by a company as a pet medication (trade name Credelio) for the treatment of tick and flea infections in dogs. The complexity of its chemical name reflects the uniqueness of its structure, namely 5- [5- (3,4,5-trichlorophenyl) -5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl] -3-methyl-thiophene-2-carboxylic acid - [2,2,2-trifluoro-ethyl-aminoformyl) - methyl] - amide. In the field of pet healthcare, Lotelana has quickly become an important drug for treating canine parasitic infections due to its high efficiency and safety.
It can quickly eliminate parasites such as tick, reticulated tick, hemochromatid tick, and blunt eyed tick that parasitize dogs, and maintain significant killing effect within one month.
On July 25, 2023, Lothilana reached an important milestone in its development journey. The US Food and Drug Administration (FDA) has approved the marketing of Lotelana eye drops (trade name Xdemvy, R&D code TP-03) developed by Tarsus Corporation for the treatment of demodex blepharitis. This is the first demodex mite treatment drug approved by the FDA that directly targets the root cause of the disease, marking a significant breakthrough for lotilana in the field of human healthcare.
Demodex induced blepharitis is a chronic inflammatory disease caused by the common human ectoparasite Demodex mites infecting the eyelid margin. Its typical clinical manifestations include itching, foreign body sensation, dry eyes, eyelid congestion, scales, and sleeve like secretions at the roots of eyelashes. In severe cases, the disease can cause complications in the conjunctiva and cornea, and has a certain degree of infectivity. In addition, Demodex mites are also one of the risk factors for meibomian gland dysfunction, which can lead to inflammation of the eyelid margin, blurred vision, meibomian gland blockage, or reduced secretion of eyelid fat.
If left untreated, it may lead to permanent changes in the tear film and progressive glandular loss.Lotelana eye drops selectively inhibit the GABA Cl channel in Demodex mites, causing paralysis and death of the mites, thereby fundamentally treating Demodex blepharitis. Its high lipophilicity helps to absorb oil from eyelash hair follicles where mites reside, improving the local efficacy of the drug.
In March 2024, Yuanda Pharmaceutical reached a strategic cooperation agreement on product introduction with Liantuo Biology and Tarsus Pharmaceuticals, and with a down payment of US $15 million and a certain amount of registration milestone fees.
Obtained the exclusive development, production and commercialization rights and interests of TP-03 in Greater China (Chinese Mainland, Hong Kong, Macao, Taiwan).This measure marks the official entry of Lotelana eye drops into the Chinese market, providing a new treatment option for Chinese patients.Previously, two key clinical studies have been completed in the United States on credelio lotilaner eye drops, involving over 800 patients with demodex blepharitis. The clinical results showed that both studies achieved the primary endpoint and all secondary endpoints with statistical significance.
And no treatment-related serious adverse events occurred.In China, the drug has also completed Phase 3 clinical trials, and the results showed that compared with the control group, the eradication rate of Demodex infection in patients with Demodex blepharitis treated with Lopina eye drops was statistically significant (p<0.001).
And the cure rate of eyelid sleeve secretion also showed a positive but not statistically significant trend (p=0.15). In addition, TP-03 has good tolerability and its safety features are similar to those observed in other large-scale clinical trials, with no treatment-related discontinuation.
references
The novel isoxazoline ectoparasiticide lotilaner (Credelio™): a non-competitive antagonist specific to invertebrates GABA-gated chloride channels, 2017
A randomized, controlled field study to assess the efficacy and safety of lotilaner flavored chewable tablets (Credelio™) in eliminating fleas in client-owned dogs, 2015
Laboratory evaluation of the efficacy and speed of kill of lotilaner (CredelioTM) against Ctenocephalides felis on cats, 2018
Comparative speed of kill provided by lotilaner (Credelio™), sarolaner (Simparica Trio™), and afoxolaner (NexGard™) to control Amblyomma americanum infestations on dogs (https://pmc.ncbi.nlm.nih.gov/articles/PMC11264992/)
FAQ
Q1: What active ingredient is contained in Credelio?
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A1: Its core active compound is lotilaner, an isoxazoline-class ectoparasiticide.
Q2: What parasites does Credelio mainly eliminate for dogs and cats?
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A2: It kills fleas and multiple common ticks for one month after single oral dose.
Q3: What is the minimum applicable age of puppies for Credelio?
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A3: The flavored oral ectoparasiticide Credelio is strictly indicated only for puppies that have reached a minimum age of 8 weeks and carry a body weight of no less than 4.4 lbs. Puppies younger than eight weeks or weighing under this standard are completely unsuitable for medication, as their liver, kidney and nervous systems remain immature and underdeveloped, which would greatly raise the risk of adverse neurological and metabolic side effects after drug intake. Therefore, breeders and pet owners must strictly follow the official age and weight threshold before giving this tick and flea treatment to young canine individuals.
304 stainless steel meets the international requirements of food grade,316 stainless steel is not only food grade or medical grade. However,the use of this medical grade as a production cup will not bring additional benefits to everyone. Why is it called 304 or 316? This is mainly defined according to the material composition. 316 stainless steel is not similar to mineral materials,after use can release some substances to promote human absorption.
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