| Primary information |
|---|
| ThPP ID | Th1088 |
| Therapeutic Peptide/Protein Name | Enfuvirtide |
| Sequence | YTSLIHSLIEESQNQQEKNEQELLELDKWASLWNWF view full sequnce in fasta |
| Functional Classification | IIa |
| Molecular Weight | 4491.876 |
| Chemical Formula | C204H301N51O64 |
| Isoelectric Point | 4.3 |
| Hydrophobicity | -0.875 |
| Melting Point (℃) | N.A. |
| Half Life | 3.8 ± 0.6 hrs |
| Description | 36 residue, synthetically prepared peptide with N-terminal acetylation and C-terminal amidation. It blocks the fusion of HIV-1 with CD4 cells. |
| Indication/Disease | Enfuvirtide is an antiretroviral drug used in combination therapy for the treatment of HIV-1/AIDS. |
| Pharmacodynamics | N.A. |
| Mechanism of Action | Enfuvirtide binds to the first heptad-repeat (HR1) in the gp41 subunit of the viral envelope glycoprotein and prevents the conformational changes required for the fusion of viral and cellular membranes. It works by disrupting the HIV-1 molecular machinery at the final stage of fusion with the target cell, preventing uninfected cells from becoming infected. Enfuvirtide is a biomimetic peptide that was rationally designed to mimic components of the HIV-1 fusion machinery and displace them, preventing normal fusion. |
| Toxicity | N.A. |
| Metabolism | Expected to undergo catabolism to its constituent amino acids, with subsequent recycling of the amino acids in the body pool. |
| Absorption | After a 90 mg single subcutaneous injection of Enfuvirtide into the abdomen in 12 HIV-1 infected subjects, the mean peak concentration is 4.59±1.5 ug/ml and the median time to peak concentration was 8 hours (ranged from 3 to12 hours). |
| Volume of Distribution | 5.5 ± 1.1 L |
| Clearance | 24.8 ± 4.1 mL/h/kg [HIV-1 infected adult and pediatric subjects following a 90-mg single SC dose of enfuvirtide] 30.6 ± 10.6 mL/h/kg [Following 90-mg twice daily dosing of FUZEON SC in combination with other antiretroviral agents in HIV-1 infected subjects] 40 ± 17 mL/h/kg [pediatric patients in the presence of concomitant medications including antiretroviral agents receiving the 2 mg/kg twice daily dose] |
| Categories | HIV Fusion Inhibitors |
| Patents Number | US6475491 |
| Date of Issue | 08/06/99 |
| Date of Expiry | 08/06/19 |
| Drug Interaction | N.A. |
| Target | N.A. |
| Information of corresponding available drug in the market |
|---|
| Brand Name | FUZEON |
| Company | Trimeris, Roche |
| Brand Discription | FUZEON (enfuvirtide) is an inhibitor of the fusion of HIV-1 with CD4 cells. Enfuvirtide is a linear 36-amino acid synthetic peptide with the N-terminus acetylated and the C-terminus is a carboxamide. It is composed of naturally occurring L-amino acid residues. Enfuvirtide is a white to off-white amorphous solid. It has negligible solubility in pure water and the solubility increases in aqueous buffers (pH 7.5) to 85-142 g/100 mL. The empirical formula of enfuvirtide is C204H301N51O64, and the molecular weight is 4492 |
| Prescribed for | FUZEON in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection in treatment experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy. |
| Chemical Name | N.A. |
| Formulation | Each single-use vial contains 108 mg of enfuvirtide for the delivery of 90 mg. Prior to subcutaneous administration, the contents of the vial are reconstituted with 1.1 mL of Sterile Water for Injection giving a volume of approximately 1.2 mL to provide the delivery of 1 mL of the solution. Each 1 mL of the reconstituted solution contains approximately 90 mg of enfuvirtide with approximate amounts of the following excipients: 22.55 mg of mannitol, 2.39 mg of sodium carbonate (anhydrous), and sodium hydroxide and hydrochloric acid for pH adjustment as needed. The reconstituted solution has an approximate pH of 9.0 |
| Physcial Appearnce | White to off-white, sterile, lyophilized powder. Each single-use vial contains 108 mg of enfuvirtide for the delivery of 90 mg. Prior to subcutaneous administration, the contents of the vial are reconstituted with 1.1 mL of Sterile Water for Injection giving a volume of approximately 1.2 mL to provi |
| Route of Administration | Subcutaneous |
| Recommended Dosage | 90 mg (1 mL) twice daily injected subcutaneously into the upper arm, anterior thigh or abdomen. Each injection should be given at a site different from the preceding injection site, and only where there is no current injection site reaction from an earlier dose. |
| Contraindication | FUZEON is contraindicated in patients with known hypersensitivity to FUZEON or any of its components |
| Side Effects | fever, chills, chest congestion, cough with yellow or green mucus, stabbing chest pain, wheezing, feeling short of breath; signs of a new infection such as sore throat, flu symptoms, swollen glands, easy bruising or bleeding. |
| Useful Link | http://www.rxlist.com/fuzeon-drug.htm http://www.drugs.com/mtm/enfuvirtide.html |
| PubMed ID | 25594223, 25553058, 24966037, 24816213, 24616600, 24500189, 24446896, 24366751 |
| 3-D Structure | Th1088 (View) or (Download) |