Peringatan Keamanan

In a clinical study in which 8 healthy subjects were administered gefapixant 1800 mg twice daily (40 times greater than the recommended dose) for up to 14 days, participants were found to have crystallized gefapixant in the urine with no additional evidence of renal or urinary system injury.L48591

Gefapixant

DB15097

small molecule approved investigational

Deskripsi

It has been estimated that 5-10% of adults globally suffer from chronic cough, which is defined as a cough lasting longer than eight weeks.L48601 A subset of these patients remain symptomatic despite thorough investigation and treatment, termed refractory chronic cough (RCC) if they have a cough that does not respond to conventional treatment or unexplained chronic cough (UCC) when no diagnosable cause for the cough can be determined.L48596 Existing treatments for chronic cough have been associated with considerable side effects, in particular opioids such as codeine or dextromethorphan.L48596

Gefapixant is a novel antagonist of the P2X3 receptor that works to reduce the cough reflex in patients with chronic cough. It received approval in both Japan and Switzerland in 2022 for the treatment of adult patients with RCC and UCC, and received subsequent approval in the EU in September 2023 for the same indications.L48596,L48591 It is the first therapy to be approved for the treatment of RCC or UCC in the EU.L48601

Struktur Molekul 2D

Berat 353.4
Wujud solid

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) The terminal half-life of gefapixant is 6-10 hours.[L48591]
Volume Distribusi Based on population pharmacokinetic analyses, the estimated steady-state apparent volume of distribution is 133.8 L (Vc 101 L and Vp 32.8 L) following oral twice-daily administration of gefapixant 45 mg.[L48596]
Klirens (Clearance) Population pharmacokinetic analyses integrating data from Phase 1, 2, and 3 data showed a geometric mean apparent clearance (Cl/F) of 10.8 L/h.[L48596] In clinical pharmacology studies, the observed clearance was 14.8 L/h and renal clearance was approximately 8.7 L/h.[L48596]

Absorpsi

The absolute bioavailability of gefapixant has not been evaluated but is estimated to be ?78%.L48596 At the recommended dose of 45 mg twice daily, steady-state is achieved within 2 days and the steady-state mean plasma AUC and Cmax are 4,144 ng?hr/mL and 531 ng/mL, respectively.L48591 The time to peak plasma concentration (Tmax) following oral administration ranges from one to four hours.L48591 The co-administration of gefapixant with a high-fat, high-calorie meal had no effect on its AUC or Cmax.L48591

Metabolisme

Gefapixant is relatively minimally metabolized. Following oral administration, only 14% of the administered dose was recovered as metabolites in the urine and feces. Unchanged parent drug is the major (87%) drug-related component in plasma, with circulating metabolites accounting for <10% each.L48591 The primary biotransformation pathways observed in gefapixant ADME studies included hydroxylation, O-demethylation, dehydrogenation, oxidation, and direct glucuronidation. Secondary biotransformation pathways included glucuronidation of O-demethylated metabolite as well as the formation of a metabolite that was O-demethylated and hydrogenated.L48596 The three most abundant circulating metabolites were: M1 (a glucuronide of O-demethylated gefapixant), M5 (a directly glucuronidated parent) and M13 (a hydroxylated metabolite.), which accounted for 1.0%, 6.3%, and 5.8%, respectively, of the total drug-related components in plasma.L48596

Rute Eliminasi

Gefapixant is primarily eliminated via renal excretion.L48591 Following a single oral radiolabeled dose in a healthy male subject, approximately 76.4% of the administered radioactivity was recovered in the urine and 22.6% was recovered in the feces.L48596,A261896 Unchanged parent drug accounted for 64% of the recovered dose in the feces and accounted for 20% of the recovered dose in the urine.L48596,A261896

Interaksi Makanan

1 Data
  • 1. Take with or without food. The administration of gefapixant with food does not result in clinically significant differences in its pharmacokinetics.

Interaksi Obat

113 Data
Nicotine The risk or severity of adverse effects can be increased when Gefapixant is combined with Nicotine.
Mecamylamine The risk or severity of adverse effects can be increased when Gefapixant is combined with Mecamylamine.
Pentolinium The risk or severity of adverse effects can be increased when Gefapixant is combined with Pentolinium.
Trimethaphan The risk or severity of adverse effects can be increased when Gefapixant is combined with Trimethaphan.
Hexamethonium The risk or severity of adverse effects can be increased when Gefapixant is combined with Hexamethonium.
Cyclopentamine The risk or severity of adverse effects can be increased when Gefapixant is combined with Cyclopentamine.
Methotrexate The protein binding of Methotrexate can be increased when combined with Gefapixant.
Ketoprofen The risk or severity of adverse effects can be increased when Ketoprofen is combined with Gefapixant.
Dexketoprofen The risk or severity of adverse effects can be increased when Dexketoprofen is combined with Gefapixant.
Cyclosporine The risk or severity of renal failure can be increased when Gefapixant is combined with Cyclosporine.
Insulin human The risk or severity of hypoglycemia can be increased when Gefapixant is combined with Insulin human.
Insulin lispro The risk or severity of hypoglycemia can be increased when Gefapixant is combined with Insulin lispro.
Insulin glargine The risk or severity of hypoglycemia can be increased when Gefapixant is combined with Insulin glargine.
Insulin pork The risk or severity of hypoglycemia can be increased when Gefapixant is combined with Insulin pork.
Troglitazone The therapeutic efficacy of Troglitazone can be increased when used in combination with Gefapixant.
Glimepiride The therapeutic efficacy of Glimepiride can be increased when used in combination with Gefapixant.
Sulfisoxazole The therapeutic efficacy of Sulfisoxazole can be increased when used in combination with Gefapixant.
Disopyramide The therapeutic efficacy of Disopyramide can be increased when used in combination with Gefapixant.
Acarbose The therapeutic efficacy of Acarbose can be increased when used in combination with Gefapixant.
Metformin The therapeutic efficacy of Metformin can be increased when used in combination with Gefapixant.
Sulfadiazine The therapeutic efficacy of Sulfadiazine can be increased when used in combination with Gefapixant.
Rosiglitazone The therapeutic efficacy of Rosiglitazone can be increased when used in combination with Gefapixant.
Acetohexamide The therapeutic efficacy of Acetohexamide can be increased when used in combination with Gefapixant.
Quinine The therapeutic efficacy of Quinine can be increased when used in combination with Gefapixant.
Miglitol The therapeutic efficacy of Miglitol can be increased when used in combination with Gefapixant.
Chlorpropamide The therapeutic efficacy of Chlorpropamide can be increased when used in combination with Gefapixant.
Nateglinide The therapeutic efficacy of Nateglinide can be increased when used in combination with Gefapixant.
Pentamidine The therapeutic efficacy of Pentamidine can be increased when used in combination with Gefapixant.
Mifepristone The therapeutic efficacy of Mifepristone can be increased when used in combination with Gefapixant.
Tolazamide The therapeutic efficacy of Tolazamide can be increased when used in combination with Gefapixant.
Repaglinide The therapeutic efficacy of Repaglinide can be increased when used in combination with Gefapixant.
Phenformin The therapeutic efficacy of Phenformin can be increased when used in combination with Gefapixant.
Sulfamethoxazole The therapeutic efficacy of Sulfamethoxazole can be increased when used in combination with Gefapixant.
Glyburide The therapeutic efficacy of Glyburide can be increased when used in combination with Gefapixant.
Glipizide The therapeutic efficacy of Glipizide can be increased when used in combination with Gefapixant.
Gliclazide The therapeutic efficacy of Gliclazide can be increased when used in combination with Gefapixant.
Tolbutamide The therapeutic efficacy of Tolbutamide can be increased when used in combination with Gefapixant.
Pioglitazone The therapeutic efficacy of Pioglitazone can be increased when used in combination with Gefapixant.
Bromocriptine The therapeutic efficacy of Bromocriptine can be increased when used in combination with Gefapixant.
Gliquidone The therapeutic efficacy of Gliquidone can be increased when used in combination with Gefapixant.
Mitiglinide The therapeutic efficacy of Mitiglinide can be increased when used in combination with Gefapixant.
Sitagliptin The therapeutic efficacy of Sitagliptin can be increased when used in combination with Gefapixant.
Sunitinib The therapeutic efficacy of Sunitinib can be increased when used in combination with Gefapixant.
Exenatide The therapeutic efficacy of Exenatide can be increased when used in combination with Gefapixant.
Mecasermin The therapeutic efficacy of Mecasermin can be increased when used in combination with Gefapixant.
Pramlintide The therapeutic efficacy of Pramlintide can be increased when used in combination with Gefapixant.
Glisoxepide The therapeutic efficacy of Glisoxepide can be increased when used in combination with Gefapixant.
Insulin aspart The risk or severity of hypoglycemia can be increased when Gefapixant is combined with Insulin aspart.
Insulin detemir The risk or severity of hypoglycemia can be increased when Gefapixant is combined with Insulin detemir.
Insulin glulisine The risk or severity of hypoglycemia can be increased when Gefapixant is combined with Insulin glulisine.
Glymidine The therapeutic efficacy of Glymidine can be increased when used in combination with Gefapixant.
AICA ribonucleotide The therapeutic efficacy of AICA ribonucleotide can be increased when used in combination with Gefapixant.
Buformin The therapeutic efficacy of Buformin can be increased when used in combination with Gefapixant.
Vildagliptin The therapeutic efficacy of Vildagliptin can be increased when used in combination with Gefapixant.
Voglibose The therapeutic efficacy of Voglibose can be increased when used in combination with Gefapixant.
NN344 The risk or severity of hypoglycemia can be increased when Gefapixant is combined with NN344.
AMG-222 The therapeutic efficacy of AMG-222 can be increased when used in combination with Gefapixant.
Bisegliptin The therapeutic efficacy of Bisegliptin can be increased when used in combination with Gefapixant.
Alogliptin The therapeutic efficacy of Alogliptin can be increased when used in combination with Gefapixant.
Dapagliflozin The therapeutic efficacy of Dapagliflozin can be increased when used in combination with Gefapixant.
Saxagliptin The therapeutic efficacy of Saxagliptin can be increased when used in combination with Gefapixant.
Liraglutide The therapeutic efficacy of Liraglutide can be increased when used in combination with Gefapixant.
Gosogliptin The therapeutic efficacy of Gosogliptin can be increased when used in combination with Gefapixant.
Linagliptin The therapeutic efficacy of Linagliptin can be increased when used in combination with Gefapixant.
Canagliflozin The therapeutic efficacy of Canagliflozin can be increased when used in combination with Gefapixant.
Glibornuride The therapeutic efficacy of Glibornuride can be increased when used in combination with Gefapixant.
Benfluorex The therapeutic efficacy of Benfluorex can be increased when used in combination with Gefapixant.
Empagliflozin The therapeutic efficacy of Empagliflozin can be increased when used in combination with Gefapixant.
Albiglutide The therapeutic efficacy of Albiglutide can be increased when used in combination with Gefapixant.
Dulaglutide The therapeutic efficacy of Dulaglutide can be increased when used in combination with Gefapixant.
Lobeglitazone The therapeutic efficacy of Lobeglitazone can be increased when used in combination with Gefapixant.
Netoglitazone The therapeutic efficacy of Netoglitazone can be increased when used in combination with Gefapixant.
Rivoglitazone The therapeutic efficacy of Rivoglitazone can be increased when used in combination with Gefapixant.
Ciglitazone The therapeutic efficacy of Ciglitazone can be increased when used in combination with Gefapixant.
Lixisenatide The therapeutic efficacy of Lixisenatide can be increased when used in combination with Gefapixant.
Insulin beef The risk or severity of hypoglycemia can be increased when Gefapixant is combined with Insulin beef.
Insulin degludec The risk or severity of hypoglycemia can be increased when Gefapixant is combined with Insulin degludec.
Insulin peglispro The risk or severity of hypoglycemia can be increased when Gefapixant is combined with Insulin peglispro.
Insulin tregopil The risk or severity of hypoglycemia can be increased when Gefapixant is combined with Insulin tregopil.
Ipragliflozin The therapeutic efficacy of Ipragliflozin can be increased when used in combination with Gefapixant.
Dutogliptin The therapeutic efficacy of Dutogliptin can be increased when used in combination with Gefapixant.
Allicin The therapeutic efficacy of Allicin can be increased when used in combination with Gefapixant.
Tofogliflozin The therapeutic efficacy of Tofogliflozin can be increased when used in combination with Gefapixant.
Ertugliflozin The therapeutic efficacy of Ertugliflozin can be increased when used in combination with Gefapixant.
2,4-thiazolidinedione The therapeutic efficacy of 2,4-thiazolidinedione can be increased when used in combination with Gefapixant.
Teneligliptin The therapeutic efficacy of Teneligliptin can be increased when used in combination with Gefapixant.
Omarigliptin The therapeutic efficacy of Omarigliptin can be increased when used in combination with Gefapixant.
Luseogliflozin The therapeutic efficacy of Luseogliflozin can be increased when used in combination with Gefapixant.
Bexagliflozin The therapeutic efficacy of Bexagliflozin can be increased when used in combination with Gefapixant.
Carmegliptin The therapeutic efficacy of Carmegliptin can be increased when used in combination with Gefapixant.
Gemigliptin The therapeutic efficacy of Gemigliptin can be increased when used in combination with Gefapixant.
Anagliptin The therapeutic efficacy of Anagliptin can be increased when used in combination with Gefapixant.
Evogliptin The therapeutic efficacy of Evogliptin can be increased when used in combination with Gefapixant.
Sotagliflozin The therapeutic efficacy of Sotagliflozin can be increased when used in combination with Gefapixant.
Balaglitazone The therapeutic efficacy of Balaglitazone can be increased when used in combination with Gefapixant.
Remogliflozin etabonate The therapeutic efficacy of Remogliflozin etabonate can be increased when used in combination with Gefapixant.
Carbutamide The therapeutic efficacy of Carbutamide can be increased when used in combination with Gefapixant.
Guar gum The therapeutic efficacy of Guar gum can be increased when used in combination with Gefapixant.
Metahexamide The therapeutic efficacy of Metahexamide can be increased when used in combination with Gefapixant.
Semaglutide The therapeutic efficacy of Semaglutide can be increased when used in combination with Gefapixant.

Target Protein

P2X purinoceptor 3 P2RX3
P2X purinoceptor 2 P2RX2

Referensi & Sumber

Synthesis reference: Hong Ren, Kevin M. Maloney, Kallol Basu, Michael J. Di Maso, Guy R. Humphrey, Feng Peng, Richard Desmond, Douglas A. L. Otte, Embarek Alwedi, Wenjun Liu, Si-Wei Zhang, Siqing Song, Rebecca A. Arvary, Michael A. Zompa, Dan Lehnherr, Gary E. Martin, Hsieh Yao D. Chang, Anne E. Mohan, Francisco J. Guzman, Lisa Jellett, Alfred Y. Lee, Glenn Spencer, Elizabeth S. Fisher, John R. Naber, Hong Gao, Sachin Lohani, Rebecca T. Ruck, and Louis-Charles Campeau. Development of a Green and Sustainable Manufacturing Process for Gefapixant Citrate (MK-7264) Part 1: Introduction and Process Overview. Organic Process Research & Development 2020 24 (11), 2445-2452. DOI:10.1021/acs.oprd.0c00248
Artikel (PubMed)
  • PMID: 35106949
    Nussbaum JC, Hussain A, Ma B, Min KC, Chen Q, Tomek C, Iwamoto M, Stoch SA: Characterization of the absorption, metabolism, excretion, and mass balance of gefapixant in humans. Pharmacol Res Perspect. 2022 Feb;10(1):e00924. doi: 10.1002/prp2.924.

Contoh Produk & Brand

Produk: 4 • International brands: 0
Produk
  • Lyfnua
    Tablet, film coated • 45 mg • Oral • EU • Approved
  • Lyfnua
    Tablet, film coated • 45 mg • Oral • EU • Approved
  • Lyfnua
    Tablet, film coated • 45 mg • Oral • EU • Approved
  • Lyfnua
    Tablet, film coated • 45 mg • Oral • EU • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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