Abstract:
: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.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Séréni D,Tubiana R,Lascoux C,Katlama C,Taulera O,Bourque A,Cohen A,Dvorchik B,Martin RR,Tournerie C,Gouyette A,Schechter PJdoi
10.1177/00912709922007552subject
Has Abstractpub_date
1999-01-01 00:00:00pages
47-54issue
1eissn
0091-2700issn
1552-4604journal_volume
39pub_type
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