Lotilaner
(Synonyms: 洛替拉纳) 目录号 : GC65292
Lotilaner 是一种杀寄生虫剂，为有效、非竞争性的昆虫 GABACl 受体拮抗剂，对果蝇 GABA 受体的 IC50 值为 23.84 nM。对家犬的 GABAA 无明显作用。
Cas No.:1369852-71-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Lotilaner is a parasiticide, acts as a potent non-competitive antagonist of insects GABACl receptors, with an IC50 of 23.84 nM for Drosophila melanogaster GABA receptor. No effect on a dog GABAA receptor[1].
Lotilaner shows IC50s of 38.25 ± 3.75, 52.40 ± 4.54, 36.79 ± 4.39 nM for Drosophila melanogaster dieldrin/fipronil-resistant forms (DmR2), Lepeophtheirus salmonis (Ls) and Rhipicephalus microplus (Rm) GABACl receptors, respectively[1].
[1]. Lotilaner, et al. The novel isoxazoline ectoparasiticide lotilaner (Credelio™): a non-competitive antagonist specific to invertebrates γ-aminobutyric acid-gated chloride channels (GABACls). Parasit Vectors. 2017 Nov 1;10(1):530.
| Cas No. | 1369852-71-0 | SDF | Download SDF |
| 别名 | 洛替拉纳 | ||
| 分子式 | C20H14Cl3F6N3O3S | 分子量 | 596.76 |
| 溶解度 | DMSO : ≥ 100 mg/mL (167.57 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.6757 mL | 8.3786 mL | 16.7572 mL |
| 5 mM | 0.3351 mL | 1.6757 mL | 3.3514 mL |
| 10 mM | 0.1676 mL | 0.8379 mL | 1.6757 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
The intravenous and oral pharmacokinetics of Lotilaner in dogs
Parasit Vectors 2017 Nov 1;10(1):522.PMID:29089051DOI:10.1186/s13071-017-2475-z.
Background: Lotilaner is a new oral ectoparasiticide from the isoxazoline class developed for the treatment of flea and tick infestations in dogs. It is formulated as pure S-enantiomer in flavoured chewable tablets (Credelio™). The pharmacokinetics of Lotilaner were thoroughly determined after intravenous and oral administration and under different feeding regimens in dogs. Methods: Twenty-six adult beagle dogs were enrolled in a pharmacokinetic study evaluating either intravenous or oral administration of Lotilaner. Following the oral administration of 20 mg/kg, under fed or fasted conditions, or intravenous administration of 3 mg/kg, blood samples were collected up to 35 days after treatment. The effects of timing of offering food and the amount of food consumed prior or after dosing on bioavailability were assessed in a separate study in 25 adult dogs. Lotilaner blood concentrations were measured using a validated liquid chromatography/tandem mass spectrometry (LC-MS/MS) method. Pharmacokinetic parameters were calculated by non-compartmental analysis. In addition, in vivo enantiomer stability was evaluated in an analytical study. Results: Following oral administration in fed animals, Lotilaner was readily absorbed and peak blood concentrations reached within 2 hours. The terminal half-life was 30.7 days. Food enhanced the absorption, providing an oral bioavailability above 80% and reduced the inter-individual variability. Moreover, the time of feeding with respect to dosing (fed 30 min prior, fed at dosing or fed 30 min post-dosing) or the reduction of the food ration to one-third of the normal daily ration did not impact bioavailability. Following intravenous administration, Lotilaner had a low clearance of 0.18 l/kg/day, large volumes of distribution Vz and Vss of 6.35 and 6.45 l/kg, respectively and a terminal half-life of 24.6 days. In addition, there was no in vivo racemization of Lotilaner. Conclusions: The pharmacokinetic properties of Lotilaner administered orally as a flavoured chewable tablet (Credelio™) were studied in detail. With a Tmax of 2 h and a terminal half-life of 30.7 days under fed conditions, Lotilaner provides a rapid onset of flea and tick killing activity with consistent and sustained efficacy for at least 1 month.
Pharmacokinetics of Lotilaner following a single oral or intravenous administration in cats
Parasit Vectors 2018 Jul 13;11(1):412.PMID:30001724DOI:10.1186/s13071-018-2966-6.
Background: CredelioTM (Lotilaner) is an oral ectoparasiticide from the isoxazoline class developed for the treatment of flea and tick infestations in cats. It is formulated as a pure S-enantiomer in flavoured chewable tablets. The pharmacokinetics of Lotilaner were investigated after intravenous or oral administration and under fed or fasted conditions in cats. Twenty-six adult cats were enrolled in a pharmacokinetic study evaluating either intravenous or oral administration of Lotilaner. Following the oral administration at a dosage of 6 mg/kg, under fed or fasted conditions, or intravenous administration of 3 mg/kg, blood samples were collected up to 35 days after treatment. Lotilaner blood concentrations were measured using a validated liquid chromatography/tandem mass spectrometry method. Pharmacokinetic parameters were calculated by non-compartmental analysis. In addition, in vivo enantiomer stability of Lotilaner was evaluated in a separate bioanalytical study. Results: Following oral administration in fed cats, Lotilaner was readily absorbed and peak blood concentrations reached within four hours. The terminal half-life was 33.6 days. Food enhanced the absorption, providing close to 100% oral bioavailability and reduced the inter-individual variability. Following intravenous administration, Lotilaner had a low clearance of 0.13 l/kg/day, large volumes of distribution Vz and Vss of 5.34 and 5.37 l/kg, respectively and a terminal half-life of 28.7 days. In addition, there was no in vivo racemization of Lotilaner. Conclusions: The pharmacokinetic properties of Lotilaner administered orally as a flavoured chewable tablet (CredelioTM) were studied in detail. With a Tmax of 4 h and a terminal half-life of 33.6 days under fed conditions, Lotilaner provides a rapid onset of flea and tick killing activity with consistent and sustained efficacy for at least one month in cats.
Efficacy of Lotilaner (Credelio™) against experimentally induced infestations of the adult cat flea, Ctenocephalides felis, and flea eggs following oral administration to cats
Parasit Vectors 2021 Mar 5;14(1):139.PMID:33673848DOI:10.1186/s13071-021-04660-2.
Background: Credelio™ (Lotilaner; Elanco) is indicated for the treatment of flea and tick infestations on cats at a recommended Lotilaner dose rate of 6-24 mg/kg. This study evaluated the efficacy and safety of Lotilaner following a single oral administration to cats for the treatment and prevention of adult Ctenocephalides felis fleas and flea egg production under laboratory conditions. Methods: Two treatment groups of ten cats each were used in this study. One group was treated with Lotilaner at a dose rate of 6-9 mg/kg on Day 0 and the other group served as the control group. Each cat was infested with 100 unfed adult fleas on days -1, 6, 13, 20 and 29. At 24 h post-treatment or post-infestation, each cat was combed to remove and count adult live fleas. At each time point, flea eggs were also collected and counted from under each cat cage. Results: Following a single oral administration of Lotilaner at a minimum dose rate of 6 mg/kg (range 6.00-8.57 mg/kg), the Lotilaner group displayed 100%, 100%, 99.9%, 99.9% and 99.8% efficacy against adult live flea counts as compared to the control group on Days 1, 7, 14, 21 and 30, respectively. At each time point, adult flea counts from the lotilaner-treated cats were significantly lower (P < 0.0001) than from the control group. A mean flea egg count of 22.6 in the lotilaner-treated cats (compared to 441.7 in the control animals) was observed 24 h post-treatment. No eggs were present from any of the treated cats on Days 7, 14 and 30 and a single egg was detected on a single treated cat on Day 21. One adverse event (regurgitated food) was observed during the study in one treated cat approximately 1 h after dosing. Conclusions: Lotilaner was well tolerated; only one adverse event was observed in the treated group. Virtually all adult fleas were killed within 24 h post-treatment or post-infestation in cats treated with a single dose of Lotilaner as compared to the control group, thus significantly reducing the number of flea eggs being produced for 30 days after treatment.
Safety of Lotilaner flavoured chewable tablets (CredelioTM) after oral administration in cats
Parasit Vectors 2018 Jul 13;11(1):409.PMID:30001745DOI:10.1186/s13071-018-2969-3.
Background: Lotilaner is a new member of the isoxazoline class for treatment of flea and tick infestations in cats. This laboratory study with Lotilaner vanilla-yeast flavoured chewable tablets (CredelioTM, Elanco) investigated the safety in healthy kittens starting at 8 weeks of age in a randomized, blinded, parallel-group design. Lotilaner tablets were given orally once a month over eight months at one, three and five times the upper level of the maximum recommended dose range (26 mg/kg). Methods: The safety of Lotilaner flavoured chewable tablets was assessed in healthy kittens when administered orally every 4 weeks for 8 months at the highest recommended dose rates, i.e. 1× (26 mg/kg) and at elevated dose rates, i.e. 3× (78 mg/kg) and 5× (130 mg/kg). Sixteen male and 16 female healthy 8-week-old kittens, with a mean body weight of 0.79 kg and 0.75 kg, respectively, were randomized to an untreated control group or Lotilaner groups at dose rates of 26 mg/kg (1×), 78 mg/kg (3×), or 130 mg/kg (5×) every four weeks over eight months. The control group was sham-dosed. All animals were fed within 30 minutes prior to treatment. Safety assessment included general health observations, detailed clinical observations, complete physical/neurological examinations, including ophthalmological examinations, electrocardiographic (ECG) and clinical pathology evaluations (haematology, clinical chemistry and urinalysis), food and water consumption, body weight, pharmacokinetic blood collections, organ macroscopic and microscopic examinations. Results: Systemic exposure to Lotilaner was confirmed during the course of the study in all treated animals with the exception of the control group. No treatment-related effects were seen on daily clinical observations, food consumption (wet), ophthalmoscopic, physical/neurological and microscopic examinations. Statistically significant differences were recorded in some of the clinical pathology parameters, body weights, food consumption (dry), electrocardiograms, and organ weights, but none of the recorded observations was considered to be of clinical relevance. Conclusions: Lotilaner, when administered once monthly over eight months at the highest recommended dose and overdoses of three- and five-fold, to 8-week-old healthy kittens, is well tolerated.
Efficacy of Lotilaner (Credelio™) against the adult cat flea, Ctenocephalides felis and flea eggs following oral administration to dogs
Parasit Vectors 2020 Jan 14;13(1):25.PMID:31937370DOI:10.1186/s13071-019-3873-1.
Background: A blinded, randomized, negative controlled laboratory study was conducted to evaluate the efficacy of Lotilaner (CredelioTM, Elanco) when administered orally to dogs, against experimentally induced adult flea infestations and flea egg production. Methods: Twenty dogs were selected for the study and allocated to two treatment groups. Ten dogs were treated with Lotilaner (at the lower half of the recommended dose range of 20-43 mg/kg) on Day 0. Ten dogs treated with placebo tablets served as the control group. Each dog was infested with 100 unfed adult C. felis fleas on days -1, 6, 13, 20 and 29. At 24 h post-treatment or post-infestation, each dog was combed for the removal and counting of adult live fleas. Flea eggs were also collected and counted from the pan under each dog cage. Results: Dogs in the Lotilaner treated group received a mean dose of 22.6 mg/kg (range 20.2-25.9 mg/kg) and no adverse events were observed in any dog in this study. At each evaluation time point, the Lotilaner group provided 100% efficacy against adult live flea counts as compared to the placebo control group. Egg production from Lotilaner treated dogs was reduced by 98.5% (geometric mean; 97.4% arithmetic mean) 24 h post-treatment (and 48 h post-flea infestation). No eggs (100% efficacy) were available for collection following infestations on Day 6 onwards from the Lotilaner treated dogs. At each evaluation time point, adult live flea counts from the Lotilaner treated dogs were significantly lower (P < 0.0001) than from the placebo control group. Conclusions: In dogs treated with a single dose of Lotilaner (mean dose 22.6 mg/kg), 100% of adult fleas were killed within 24 h post-treatment or post-subsequent infestations as compared to the placebo control group, thereby demonstrating that Lotilaner kills fleas before they can lay eggs thus preventing subsequent flea infestations for 30 days after treatment. There were no reported adverse events in any dogs, demonstrating that Lotilaner tablets were well tolerated at the dose rates assessed in this study.