[Enfuvirtide, first fusion inhibitor in the treatment of human immunodeficiency virus infection: mechanism of action and pharmacokinetics].
Enfuvirtide is a 36 amino-acid synthetic peptide derived from the HR2 sequence of the HIV-1 gp41. Enfuvirtide is different from other antiretroviral drugs by its extra-cellular action where it binds to the HR1 domain at the viral surface of the gp41. The drug inhibits the conformational change of the glycoprotein, preventing the intimate fusion between the HIV envelope and the CD4 cell membrane and finally the penetration of the viral capside into the target cells. Following a 90 mg subcutaneous injection, the plasma concentration rises rapidly to reach a 4.59 +/- 1.5 microg/ml Cmax between 5 and 7 hours. Residual concentrations are between 2.6 and 3.4 microg/ml and the bioavailability of the drug is approximately 80%. Plasma concentrations and area under curve are dose-dependant. The site of injection does not influence the pharmacokinetic parameters of the drug. Infuvirtide is not an inhibitor of the P450 cytochrome and no pharmacokinetic interactions have been reported with P450 metabolised drugs.
Raffi
François
F
Service des maladies infectieuses et tropicales, Hôtel-Dieu CHU, place Alexis-Ricordeau, 44093 Nantes cedex 1, France. francois.raffi@chu-nantes.fr
D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000378:metabolism / Q000494:pharmacology*; D023581:HIV Fusion Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D010446:Peptide Fragments / Q000493:pharmacokinetics* / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D000077560:Enfuvirtide