A fusion inhibitor (FP-21399) for the treatment of human immunodeficiency virus infection: a phase I study.

Abstract

FP-21399 is a bis(disulfonaphthalene) derivative that prevents human immunodeficiency virus (HIV) infection of uninfected cells by blocking entry of the virus. FP-21399 shows an affinity for lymph nodes. In this phase I study, FP-21399 was administered intravenously over 1 h as a single dose (0.9, 1.7, 2.8, and 4.2 mg/kg) or as a once-weekly infusion (1, 2, and 3 mg/kg) for 4 consecutive weeks to 34 HIV-1 infected patients with CD4(+) cell counts of 50-400 cells/microL. Concomitant antiretroviral therapy was permitted but not required. The most frequent adverse events involved the transient, dose-dependent appearance of drug- or metabolite-related color in the urine and skin. Plasma drug levels were linear with dose. The drug was cleared, with an elimination half-life of 4 h and a terminal half-life of 1.5-2 days; the terminal half-life represented redistribution and clearance from tissues. FP-21399 administered weekly for 4 weeks was well tolerated. Further studies are necessary to define the role of this fusion inhibitor in the treatment of HIV infection.

• Authors: B J Dezube, T A Dahl, T K Wong, B Chapman, M Ono, N Yamaguchi, S D Gillies, L B Chen, C S Crumpacker
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 182 Issue 2 Pg. 607-10 (Aug 2000) ISSN: 0022-1899 [Print] United States
• PMID: 10915097 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-HIV Agents
• Chlorobenzenes
• Naphthalenes
• FP 21399

Topics

• Adult
• Anti-HIV Agents (pharmacokinetics, therapeutic use)
• Cell Fusion (drug effects)
• Chlorobenzenes (pharmacokinetics, therapeutic use)
• Female
• HIV Infections (drug therapy)
• Humans
• Male
• Middle Aged
• Naphthalenes (pharmacokinetics, therapeutic use)