Pharmacokinetics and tolerability of intravenous trecovirsen (GEM 91), an antisense phosphorothioate oligonucleotide, in HIV-positive subjects

J Clin Pharmacol. 1999 Jan;39(1):47-54. doi: 10.1177/00912709922007552.


Trecovirsen, a 25-mer antisense phosphorothioate oligonucleotide targeted at the gag site of the HIV gene, was administered to HIV-positive volunteers as an i.v. infusion. Single doses ranged from 0.1 to 2.5 mg/kg in an ascending escalation in cohorts of 6 to 12 subjects. Plasma trecovirsen concentrations and pharmacokinetic parameters could be assessed at doses > or = 0.3 mg/kg. Peak plasma concentrations and AUC values increased disproportionately with increasing dose while elimination half-life increased and plasma clearance decreased, indicating a saturable process over this dose range. The only significant adverse event observed was an isolated, transitory increase in activated partial thromboplastin time at doses > or = 2.0 mg/kg that was related to plasma trecovirsen concentrations and is attributed to the polyanionic character of the molecule. Thus, trecovirsen administration was well tolerated in single i.v. doses up to 2.5 mg/kg.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / pharmacokinetics*
  • Area Under Curve
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Female
  • HIV Seropositivity / drug therapy*
  • Headache / chemically induced
  • Humans
  • Infusions, Intravenous
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Oligodeoxyribonucleotides, Antisense / adverse effects
  • Oligodeoxyribonucleotides, Antisense / pharmacokinetics*
  • Partial Thromboplastin Time
  • Thionucleotides / adverse effects
  • Thionucleotides / pharmacokinetics*


  • Anti-HIV Agents
  • Oligodeoxyribonucleotides, Antisense
  • Thionucleotides
  • GEM91