Lenacapavir (GS-6207) is the first HIV-1 capsid inhibitor approved by the U.S. Food and Drug Administration, the European Medicines Agency, and Health Canada for the treatment of MDR HIV-1 infection.[3]

Anti-HIV:100 pM (EC50), MT-4 cells:100 pM (EC50)

The half-maximal effective concentration (EC50) of lenacapavir in MT-4 cells is 105 pmol/L; the half-maximal effective concentration (EC50) in primary human CD4 cells is 32 pmol/L; and the half-maximal effective concentration (EC50) in macrophages is 56 pmol/L. [1]

The pharmacokinetics of lenacapavir after a single oral dose are nonlinear and dose-proportional over the dose range of 50-1800 mg, whereas they are dose-proportional when administered subcutaneously at 309-927 mg. The median half-life after oral and subcutaneous administration is 10 to 12 days and 8 to 12 weeks, respectively. The bioavailability of oral lenacapavir is 6-10%, with peak concentrations measured after 4 hours. Subcutaneous lenacapavir is completely absorbed and slowly released from the injection site, with peak plasma concentrations reached 84 days after administration. After a single subcutaneous dose of 900 mg, plasma concentrations remain well above the response threshold for more than 6 months, but oral lenacapavir is used for the initial loading phase because of slow initial diffusion into the circulation. The volume of distribution of lenacapavir is 976 L, and the drug is 99.8% protein bound, as calculated from a population PK study. [2]