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| 1mg |
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| 10mg |
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| 50mg |
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Atogepant (MK-8031; MK8031; Qulipta), a gepant, is a novel, oral and potent calcitonin gene-related peptide receptor antagonist approved in September 2021 for medical use in the United States to prevent episodic migraines.
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
The time to peak plasma concentration following oral administration is approximately 2-3 hours. Atogepant displays dose-proportional pharmacokinetics up to approximately 3-fold its recommended maximum dosage, and its pharmacokinetics are not significantly influenced by co-administration with food. The elimination of atogepant occurs primarily via metabolism by CYP3A4. Following a single oral dose of radiolabeled atogepant to healthy male subjects, 42% of the administered dose was recovered as unchanged parent drug in the feces and 5% as unchanged parent drug in the urine. In total, approximately 81% of the radioactivity was recovered in the feces, with only 8% recovered in the urine. The mean apparent volume of distribution of atogepant is 292 L. The mean apparent oral clearance of atogepant is approximately 19 L/h. Metabolism / Metabolites The metabolism of atogepant is mediated primarily via CYP3A4. The most prevalent circulating compounds in plasma are atogepant itself and a glucuronide conjugate metabolite (M23), comprising approximately 75% and 15% of the administered dose, respectively, with at least 10 other metabolites detected in feces representing <10% of the administered dose. Biological Half-Life The elimination half-life of atogepant following oral administration is approximately 11 hours. |
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| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation Because there is no published experience with atogepant during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding Atogepant is extensively (~95.3%) protein-bound in plasma. |
| References | |
| Additional Infomation |
Pharmacodynamics
Atogepant helps to prevent migraine headaches by antagonizing the activity of a pronociceptive molecule (CGRP) which has been implicated in migraine pathophysiology. Intended for preventative use, rather than abortive migraine therapy, atogepant is administered once daily. While no dose adjustments are required for patients with mild or moderate hepatic impairment, atogepant should be avoided in patients with severe hepatic impairment. Similarly, no dose adjustments are required for patients with mild or moderate renal impairment, but patients with severe renal impairment should be limited to a maximum daily dose of 10mg. |
| Molecular Formula |
C29H23F6N5O3
|
|---|---|
| Molecular Weight |
603.5254
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| Exact Mass |
603.17
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| CAS # |
1374248-81-3
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| Related CAS # |
(3R,5R,6S)-Atogepant
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| PubChem CID |
72163100
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
693.9±55.0 °C at 760 mmHg
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| Flash Point |
373.5±31.5 °C
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| Vapour Pressure |
0.0±2.2 mmHg at 25°C
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| Index of Refraction |
1.624
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| LogP |
4.37
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| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
4
|
| Heavy Atom Count |
43
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| Complexity |
1110
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| Defined Atom Stereocenter Count |
4
|
| SMILES |
C[C@@H]1[C@@H](C[C@@H](C(=O)N1CC(F)(F)F)NC(=O)C2=CC3=C(C[C@@]4(C3)C5=C(NC4=O)N=CC=C5)N=C2)C6=C(C=CC(=C6F)F)F
|
| InChi Key |
QIVUCLWGARAQIO-OLIXTKCUSA-N
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| InChi Code |
InChI=1S/C29H23F6N5O3/c1-13-16(22-18(30)4-5-19(31)23(22)32)8-20(26(42)40(13)12-29(33,34)35)38-25(41)15-7-14-9-28(10-21(14)37-11-15)17-3-2-6-36-24(17)39-27(28)43/h2-7,11,13,16,20H,8-10,12H2,1H3,(H,38,41)(H,36,39,43)/t13-,16-,20+,28+/m1/s1
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| Chemical Name |
(3'S)-N-[(3S,5S,6R)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,6-trifluorophenyl)piperidin-3-yl]-2'-oxo-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridine]-3-carboxamide
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| Synonyms |
MK8031 MK-8031 MK8031 Atogepant.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~165.69 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6569 mL | 8.2846 mL | 16.5692 mL | |
| 5 mM | 0.3314 mL | 1.6569 mL | 3.3138 mL | |
| 10 mM | 0.1657 mL | 0.8285 mL | 1.6569 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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