A fusion inhibitor (FP-21399) for the treatment of human immunodeficiency virus infection: a phase I study.
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.
Dezube
B J
BJ
Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. bdezube@caregroup.harvard.edu
Dahl
T A
TA
Wong
T K
TK
Chapman
B
B
Ono
M
M
Yamaguchi
N
N
Gillies
S D
SD
Chen
L B
LB
Crumpacker
C S
CS
D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002459:Cell Fusion / Q000187:drug effects*; D002722:Chlorobenzenes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000493:pharmacokinetics / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D002722:Chlorobenzenes; D009281:Naphthalenes; C106790:FP 21399