Aprepitant
Overview
Description
Aprepitant is a medication primarily used to prevent chemotherapy-induced nausea and vomiting, as well as postoperative nausea and vomiting . It belongs to the class of neurokinin-1 receptor antagonists and works by blocking the action of substance P, a neuropeptide associated with vomiting . This compound is marketed under the brand name Emend, among others .
Mechanism of Action
Target of Action
Aprepitant is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors . It has little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors .
Mode of Action
this compound works by blocking the action of a natural substance in the brain called neurokinin . It has been shown in animal models to inhibit emesis induced by cytotoxic chemotherapeutic agents, such as cisplatin, via central actions . Positron Emission Tomography (PET) studies with this compound have shown that it crosses the blood-brain barrier and occupies brain NK1 receptors .
Biochemical Pathways
this compound primarily undergoes CYP3A4-mediated metabolism, with minor metabolism mediated by CYP1A2 and CYP2C19 . About seven metabolites of this compound have been identified in human plasma, all of which retain weak pharmacological activity . In addition to being a substrate, this compound has been shown to moderately inhibit CYP3A4 and mildly induce CYP2C9 .
Pharmacokinetics
this compound has a bioavailability of 60–65% . It is highly protein-bound (>95%) and is metabolized in the liver, mostly by CYP3A4, with some contributions by CYP2C19 and CYP1A2 . The elimination half-life of this compound is 9–13 hours, and it is excreted via the kidneys (57%) and feces (45%) .
Result of Action
this compound has been shown to have multiple antitumor actions against many types of cancer . It significantly inhibits the excitability of Dorsal Root Ganglion (DRG) neurons . The pain behavior and the paw tissues inflammatory damage were significantly relieved after the administration of this compound . This compound significantly suppressed the activation of microglia, phosphorylation of JNK and p38 MAPK, as well as the mRNA and protein expressions of MCP-1, TNF-α, IL-6, and IL-1β, in vivo and in vitro .
Action Environment
Environmental factors can influence the action of this compound. For example, in cancer cells, this compound increases the sensitization of these cells to the cytotoxic action of certain substances . It impairs the interaction of Forkhead box M1 with beta-catenin, leading to the blockade of the Wnt canonical pathway . It arrests the G2 cell cycle, promoting apoptosis .
Biochemical Analysis
Biochemical Properties
Aprepitant interacts with the NK1 receptors, blocking the signals given off by these receptors . It has little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors .
Cellular Effects
This compound has been shown to inhibit the proliferation, migration, and invasion of gallbladder cancer cells . It also significantly boosts the apoptosis, reactive oxygen species (ROS), and inflammation response in gallbladder cancer .
Molecular Mechanism
This compound works by blocking substance P from attaching to the NK1 receptors . This decreases the likelihood of vomiting in patients . It is classified as an NK1 antagonist because it blocks signals given off by NK1 receptors .
Temporal Effects in Laboratory Settings
This compound provides protection against nausea and vomiting over multiple cycles of cisplatin-based chemotherapy . It has been shown to enhance control of chemotherapy-induced nausea and vomiting (CINV) over time .
Dosage Effects in Animal Models
In animal models, this compound has been shown to have anti-inflammatory and antioxidant properties . The effects of this compound on the lung tissues of rats with an experimental polymicrobial sepsis model were examined, and it was found that this compound effectively inhibited the proliferation, migration, and invasion of these cells .
Metabolic Pathways
This compound primarily undergoes CYP3A4-mediated metabolism, as well as minor metabolism mediated by CYP1A2 and CYP2C19 . About seven metabolites of this compound have been identified in human plasma, which all retain weak pharmacological activity .
Transport and Distribution
This compound is generally safe and well tolerated in healthy subjects. Its pharmacokinetics is comparable between different ethnicities following single-dose administration . The pharmacokinetics following a clinical 3-day regimen on healthy subjects has been characterized .
Preparation Methods
Synthetic Routes and Reaction Conditions: Aprepitant is synthesized through a multi-step process involving several key intermediates. The synthesis typically starts with the preparation of a morpholine derivative, which is then subjected to various chemical reactions, including alkylation, acylation, and cyclization . The final product is obtained through purification and crystallization steps to ensure high purity and yield .
Industrial Production Methods: In industrial settings, the production of this compound involves optimizing the reaction conditions to maximize yield and minimize impurities. Techniques such as high-performance liquid chromatography (HPLC) and gas chromatography (GC) are used to monitor the reaction progress and ensure the quality of the final product . Additionally, advanced formulation techniques, such as nanoprecipitation and solid dispersion, are employed to enhance the solubility and bioavailability of this compound .
Chemical Reactions Analysis
Types of Reactions: Aprepitant undergoes various chemical reactions, including oxidation, reduction, and substitution . These reactions are essential for modifying the chemical structure and improving the pharmacological properties of the compound.
Common Reagents and Conditions: Common reagents used in the synthesis of this compound include alkylating agents, acylating agents, and reducing agents . The reactions are typically carried out under controlled conditions, such as specific temperatures, pressures, and pH levels, to ensure optimal yields and minimal side reactions .
Major Products Formed: The major products formed from the chemical reactions of this compound include its various intermediates and the final active pharmaceutical ingredient (API) . These products are characterized using techniques such as nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), and infrared (IR) spectroscopy to confirm their structures and purities .
Scientific Research Applications
Chemotherapy-Induced Nausea and Vomiting (CINV)
Overview
Aprepitant is predominantly used in combination with other antiemetic agents to manage CINV, especially in patients receiving highly emetogenic chemotherapy. The drug's efficacy has been established through multiple clinical trials.
Efficacy Data
A systematic review highlighted the effectiveness of this compound in preventing CINV. In a phase III study, patients receiving this compound demonstrated a complete response rate of 83.2% compared to 71.3% in the control group (P < 0.05) .
| Study | Treatment Group | Complete Response Rate (%) | Control Group Response Rate (%) |
|---|---|---|---|
| Hesketh et al., 2003 | This compound + standard therapy | 83.2 | 71.3 |
| Poli-Bigelli et al., 2003 | This compound + standard therapy | 62 | 52 |
Antitumor Effects
Mechanism of Action
Recent studies have indicated that this compound may possess antitumor properties. Research has shown that it induces apoptosis in tumor cells and can reduce tumor volume in animal models .
Case Studies
In preclinical trials involving human osteosarcoma and hepatoblastoma xenografts, this compound significantly decreased tumor size when administered alongside conventional therapies .
Dermatological Applications
Topical Use
this compound has been explored for its topical application to mitigate side effects associated with other cancer treatments, such as erlotinib-induced dermatitis and hair loss. In a study involving rats, topical administration of this compound resulted in up to a 70% reduction in neutrophil activity related to inflammation caused by erlotinib .
| Treatment Group | Neutrophil Activity Reduction (%) |
|---|---|
| Control | Baseline |
| Low Dose | 24% reduction |
| High Dose | 70% reduction |
Potential Use in Other Conditions
Pruritus Management
Emerging research suggests that this compound may be effective in treating pruritus (itching) associated with various conditions, particularly in cancer patients .
Antiviral Properties
Studies have also hinted at the antiviral effects of this compound, suggesting its potential use against certain viral infections by modulating immune responses .
Comparison with Similar Compounds
Aprepitant is often compared with other antiemetic agents, such as ondansetron and dexamethasone . While ondansetron is a serotonin (5-HT3) receptor antagonist and dexamethasone is a corticosteroid, this compound is unique in its mechanism of action as an NK1 receptor antagonist . This distinct mechanism allows this compound to complement traditional antiemetic drugs and enhance the control of chemotherapy-induced nausea and vomiting . Other similar compounds include fosthis compound, a prodrug of this compound, which is converted to this compound in the body and shares the same mechanism of action .
Biological Activity
Aprepitant is a neurokinin-1 (NK-1) receptor antagonist primarily used for the prevention of chemotherapy-induced nausea and vomiting (CINV). Recent research has expanded its potential applications, particularly in oncology, where it has shown promise as an anticancer agent. This article delves into the biological activity of this compound, highlighting its mechanisms of action, efficacy in clinical studies, and emerging roles in cancer therapy.
This compound functions by selectively blocking the NK-1 receptors in the central nervous system, which are activated by substance P, a neuropeptide involved in the vomiting reflex. By inhibiting these receptors, this compound effectively reduces both acute and delayed phases of CINV induced by chemotherapeutic agents such as cisplatin .
Recent studies have revealed additional mechanisms through which this compound exerts its effects:
- Induction of Immunogenic Cell Death : this compound has been shown to activate the anticipatory unfolded protein response (a-UPR), leading to necrotic cell death that stimulates immune responses. This process involves the release of damage-associated molecular patterns (DAMPs), such as HMGB1 and ATP, which enhance macrophage migration and activation .
- Calcium Release and Stress Response Activation : The drug appears to trigger calcium release from the endoplasmic reticulum, resulting in hyperactivation of stress response pathways that contribute to its anticancer effects .
Chemotherapy-Induced Nausea and Vomiting (CINV)
A meta-analysis encompassing 23 randomized controlled trials with 7,956 patients demonstrated that this compound-containing regimens significantly improved complete response rates for CINV compared to standard therapies. The results indicated:
- Complete Response Rates : 50.3% in standard therapy vs. 66.4% and 70.5% in this compound 40/25 mg and 125/80 mg groups respectively .
- Safety Profile : No significant differences in severe adverse events were noted between groups; however, higher incidences of fatigue and hiccups were observed in the this compound group .
Case Studies
A case study reported successful outcomes using this compound for refractory postoperative nausea and vomiting, suggesting its utility beyond traditional applications .
Efficacy Against Cancer Cells
Recent preclinical studies have established that this compound not only alleviates nausea but also induces cell death in various cancer types:
- Breast Cancer Models : this compound treatment resulted in typical features of necrotic cell death, including cell swelling and membrane rupture. This mode of action was confirmed through both 2D cell culture and 3D organoid models .
Summary of Key Trials
| Study Type | Population | Treatment Regimen | Complete Response Rate | Adverse Events |
|---|---|---|---|---|
| Phase II | Japanese cancer patients | This compound + standard therapy | 70.5% (highest) | Similar to standard therapy |
| Meta-analysis | 7,956 patients | This compound-containing regimens | Significantly improved vs. control | Higher fatigue incidence |
| Case Study | Post-operative patients | This compound for refractory nausea | Improvement noted | Not specified |
Properties
IUPAC Name |
3-[[(2R,3S)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholin-4-yl]methyl]-1,4-dihydro-1,2,4-triazol-5-one |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C23H21F7N4O3/c1-12(14-8-15(22(25,26)27)10-16(9-14)23(28,29)30)37-20-19(13-2-4-17(24)5-3-13)34(6-7-36-20)11-18-31-21(35)33-32-18/h2-5,8-10,12,19-20H,6-7,11H2,1H3,(H2,31,32,33,35)/t12-,19+,20-/m1/s1 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
ATALOFNDEOCMKK-OITMNORJSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
CC(C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)OC2C(N(CCO2)CC3=NNC(=O)N3)C4=CC=C(C=C4)F |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Isomeric SMILES |
C[C@H](C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)O[C@@H]2[C@@H](N(CCO2)CC3=NNC(=O)N3)C4=CC=C(C=C4)F |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C23H21F7N4O3 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID3049047 |
Source
|
| Record name | Aprepitant | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID3049047 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
534.4 g/mol |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Physical Description |
Solid |
Source
|
| Record name | Aprepitant | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014811 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
Solubility |
Practically insoluble, 1.94e-02 g/L |
Source
|
| Record name | Aprepitant | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00673 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
| Record name | Aprepitant | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014811 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
Mechanism of Action |
Aprepitant has been shown in animal models to inhibit emesis induced by cytotoxic chemotherapeutic agents, such as cisplatin, via central actions. Animal and human Positron Emission Tomography (PET) studies with Aprepitant have shown that it crosses the blood brain barrier and occupies brain NK1 receptors. Animal and human studies show that Aprepitant augments the antiemetic activity of the 5-HT3-receptor antagonist ondansetron and the corticosteroid ethasone and inhibits both the acute and delayed phases of cisplatin induced emesis. |
Source
|
| Record name | Aprepitant | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00673 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
CAS No. |
170729-80-3 |
Source
|
| Record name | Aprepitant | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=170729-80-3 | |
| Description | CAS Common Chemistry is an open community resource for accessing chemical information. Nearly 500,000 chemical substances from CAS REGISTRY cover areas of community interest, including common and frequently regulated chemicals, and those relevant to high school and undergraduate chemistry classes. This chemical information, curated by our expert scientists, is provided in alignment with our mission as a division of the American Chemical Society. | |
| Explanation | The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated. | |
| Record name | Aprepitant [USAN:INN:JAN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0170729803 | |
| Description | ChemIDplus is a free, web search system that provides access to the structure and nomenclature authority files used for the identification of chemical substances cited in National Library of Medicine (NLM) databases, including the TOXNET system. | |
| Record name | Aprepitant | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00673 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
| Record name | Aprepitant | |
| Source | DTP/NCI | |
| URL | https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=748825 | |
| Description | The NCI Development Therapeutics Program (DTP) provides services and resources to the academic and private-sector research communities worldwide to facilitate the discovery and development of new cancer therapeutic agents. | |
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| Record name | Aprepitant | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID3049047 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | Aprepitant | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/information-on-chemicals | |
| Description | The European Chemicals Agency (ECHA) is an agency of the European Union which is the driving force among regulatory authorities in implementing the EU's groundbreaking chemicals legislation for the benefit of human health and the environment as well as for innovation and competitiveness. | |
| Explanation | Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page. | |
| Record name | APREPITANT | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/1NF15YR6UY | |
| Description | The FDA Global Substance Registration System (GSRS) enables the efficient and accurate exchange of information on what substances are in regulated products. Instead of relying on names, which vary across regulatory domains, countries, and regions, the GSRS knowledge base makes it possible for substances to be defined by standardized, scientific descriptions. | |
| Explanation | Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required. | |
| Record name | Aprepitant | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014811 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
Retrosynthesis Analysis
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Strategy Settings
| Precursor scoring | Relevance Heuristic |
|---|---|
| Min. plausibility | 0.01 |
| Model | Template_relevance |
| Template Set | Pistachio/Bkms_metabolic/Pistachio_ringbreaker/Reaxys/Reaxys_biocatalysis |
| Top-N result to add to graph | 6 |
Feasible Synthetic Routes
Q1: What is the primary mechanism of action of aprepitant?
A1: this compound exerts its antiemetic effect by acting as a selective antagonist of the neurokinin-1 (NK-1) receptor. [, , , , ] This receptor, primarily located in the central nervous system (CNS), is the primary binding site for substance P, a neuropeptide involved in the transmission of nausea and vomiting signals. [, , ] By blocking substance P from binding to NK-1 receptors, this compound effectively disrupts the emetic pathway. []
Q2: What makes this compound particularly effective against delayed CINV?
A2: this compound demonstrates prolonged NK-1 receptor occupancy in the CNS, lasting at least 48 hours after a single dose of its prodrug fosthis compound. [, ] This sustained receptor blockade effectively controls delayed CINV, which typically manifests 2 to 5 days post-chemotherapy. []
Q3: Does this compound affect gastric emptying?
A3: While this compound effectively controls nausea, there is evidence suggesting that it does not significantly accelerate gastric emptying. [] This suggests its antiemetic action is primarily mediated through central NK-1 receptor antagonism rather than by directly influencing gastric motility.
Q4: What is the molecular formula and weight of this compound?
A4: Unfortunately, the provided research papers do not explicitly state the molecular formula and weight of this compound. For detailed structural information, it is recommended to consult additional resources like PubChem or DrugBank databases.
Q5: What is fosthis compound, and how does it relate to this compound?
A5: Fosthis compound is a water-soluble prodrug of this compound, meaning it is converted into active this compound in the body. [, , , , , ] It is administered intravenously and rapidly metabolized into this compound via ubiquitous phosphatases within 30 minutes of administration. [, ] This makes it a suitable alternative for patients who have difficulty tolerating oral medications. [, , ]
Q6: How is this compound metabolized?
A6: this compound undergoes extensive metabolism, primarily by cytochrome P450 (CYP) 3A4 enzymes. [, , , , ] It is first metabolized into the active N-dealkylated metabolite (ND-AP), which is further converted into its carbonyl form (ND-CAP). []
Q7: Does food intake influence the bioavailability of this compound?
A7: Studies indicate that food does not significantly impact the bioavailability of a single oral dose of this compound, suggesting dose adjustments based on food intake are unnecessary. []
Q8: What is the relationship between this compound exposure and total bilirubin levels?
A8: A study investigating this compound pharmacokinetics in cancer patients revealed a significant correlation between the 120-hour area under the curve (AUC) of this compound and total bilirubin levels. [] This suggests that liver function may influence this compound exposure, but further investigation is needed to fully elucidate this relationship.
Q9: What are the approved clinical applications of this compound and fosthis compound?
A9: Both this compound and fosthis compound are FDA-approved for preventing CINV in patients undergoing highly emetogenic chemotherapy, typically in combination with a corticosteroid (like dexamethasone) and a 5-HT3 receptor antagonist (like ondansetron). [, , , , , , , ]
Q10: Can a single dose of fosthis compound effectively prevent CINV?
A10: Yes, clinical trials have demonstrated that a single intravenous dose of fosthis compound (150 mg) is noninferior to the standard 3-day this compound regimen for preventing both acute and delayed CINV in patients receiving high-dose cisplatin. [, , ]
Q11: Is this compound effective in preventing CINV in pediatric patients?
A11: While further research is necessary, studies suggest that this compound, in combination with standard antiemetic therapy, can be effective in reducing CINV in children and adolescents. [, , , ] One study even reported the safe use of this compound in children as young as 11 months old. []
Q12: Are there alternative antiemetic regimens to this compound for CINV?
A12: A fixed-dose combination of netupitant (another NK-1 receptor antagonist) and palonosetron (a 5-HT3 receptor antagonist), known as NEPA, has shown comparable efficacy to a 3-day this compound regimen in preventing CINV associated with moderately emetogenic chemotherapy. []
Q13: Does this compound interact with other medications?
A13: Yes, this compound is metabolized by CYP3A4 and can both inhibit and induce this enzyme, potentially leading to drug interactions. [, , , , ] For instance, this compound can increase the plasma concentrations of dexamethasone and methylprednisolone. [, , ] It can also decrease the plasma concentrations of drugs metabolized by CYP3A4, such as warfarin and hormonal contraceptives. [, , ]
Q14: Does this compound interact with vincristine?
A14: While this compound does not appear to cause a clinically significant drug interaction with vincristine that leads to early-onset peripheral neuropathy, there seems to be an increased risk of overall chemotherapy-induced peripheral neuropathy (CIPN) with concomitant use. [] Further research is needed to fully understand this potential interaction.
Q15: Does this compound affect prednisolone pharmacokinetics?
A15: A study investigating the co-administration of this compound with the R-CHOP chemotherapy regimen, which includes prednisolone, found no significant impact of this compound on prednisolone pharmacokinetics. [] This is consistent with previous findings that CYP3A4 inhibitors, like ketoconazole and itraconazole, do not affect prednisolone metabolism, unlike their effect on dexamethasone and methylprednisolone. []
Q16: How does this compound interact with voriconazole?
A16: this compound initially inhibits voriconazole metabolism due to its triazole ring, but subsequently induces CYP3A4, leading to increased voriconazole metabolism and potentially subtherapeutic drug levels. [] This interaction highlights the importance of monitoring voriconazole levels when co-administered with this compound or fosthis compound.
Q17: Are there any potential antitumor effects of this compound?
A17: While currently used as an antiemetic, preclinical studies suggest that this compound may possess antitumor properties through various mechanisms, including antiproliferative, antimetastatic, and pro-apoptotic effects. [, ] Further research is warranted to explore these findings and assess the potential of repurposing this compound as an anticancer agent.
Q18: Does this compound have any immunomodulatory effects?
A18: Research suggests that this compound may possess immunomodulatory properties by decreasing the expression of programmed death 1 (PD-1) on CD4+ T cells and reducing plasma levels of substance P and soluble CD163. [] This indicates a potential role of NK-1 receptor antagonism in modulating monocyte activation during HIV infection, warranting further investigation.
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