Pharmacokinetics of an anti-human immunodeficiency virus antisense oligodeoxynucleotide phosphorothioate (GEM 91) in HIV-infected subjects

Ruiwen Zhang, Jieming Yan, Harout Shahinian, Girish Amin, Zhihong Lu, Tiepu Liu, Michael S. Saag, Zhiwei Jiang, Jamal Temsamani, R. Russell Martin, Paul J. Schechter, Sudhir Agrawal, Robert B Diasio

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Abstract

Human pharmacokinetics of an antisense oligodeoxynucleotide phosphorothioate (GEM 91) developed as an anti-human immunodeficiency virus (HIV) agent was carried out in this study. 35S-Labeled GEM 91 was administered to six HIV-infected individuals by means of 2-hour intravenous infusions at a dose of 0.1 mg/kg. Plasma disappearance curves for GEM 91-derived radioactivity could be described by the sum of two exponentials, with half-life values of 0.18 ± 0.04 and 26.71 ± 1.67 hours. The radioactivity in plasma was further evaluated by polyacrylamide gel electrophoresis, showing the presence of both intact GEM 91 and lower molecular weight metabolites. Urinary excretion represented the major pathway of elimination, with 49.15% ± 6.80% of the administered dose excreted within 24 hours and 70.37% ± 6.72% over 96 hours after dosing. The radioactivity in urine was associated with lower molecular weight metabolites. No drug-related toxicity was observed.

Original languageEnglish (US)
Pages (from-to)44-53
Number of pages10
JournalClinical Pharmacology and Therapeutics
Volume58
Issue number1
DOIs
StatePublished - 1995
Externally publishedYes

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Oligodeoxyribonucleotides
Pharmacokinetics
HIV
Radioactivity
Molecular Weight
Drug-Related Side Effects and Adverse Reactions
Intravenous Infusions
Half-Life
Polyacrylamide Gel Electrophoresis
Urine
GEM91

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Pharmacokinetics of an anti-human immunodeficiency virus antisense oligodeoxynucleotide phosphorothioate (GEM 91) in HIV-infected subjects. / Zhang, Ruiwen; Yan, Jieming; Shahinian, Harout; Amin, Girish; Lu, Zhihong; Liu, Tiepu; Saag, Michael S.; Jiang, Zhiwei; Temsamani, Jamal; Russell Martin, R.; Schechter, Paul J.; Agrawal, Sudhir; Diasio, Robert B.

In: Clinical Pharmacology and Therapeutics, Vol. 58, No. 1, 1995, p. 44-53.

Research output: Contribution to journalArticle

Zhang, R, Yan, J, Shahinian, H, Amin, G, Lu, Z, Liu, T, Saag, MS, Jiang, Z, Temsamani, J, Russell Martin, R, Schechter, PJ, Agrawal, S & Diasio, RB 1995, 'Pharmacokinetics of an anti-human immunodeficiency virus antisense oligodeoxynucleotide phosphorothioate (GEM 91) in HIV-infected subjects', Clinical Pharmacology and Therapeutics, vol. 58, no. 1, pp. 44-53. https://doi.org/10.1016/0009-9236(95)90071-3
Zhang, Ruiwen ; Yan, Jieming ; Shahinian, Harout ; Amin, Girish ; Lu, Zhihong ; Liu, Tiepu ; Saag, Michael S. ; Jiang, Zhiwei ; Temsamani, Jamal ; Russell Martin, R. ; Schechter, Paul J. ; Agrawal, Sudhir ; Diasio, Robert B. / Pharmacokinetics of an anti-human immunodeficiency virus antisense oligodeoxynucleotide phosphorothioate (GEM 91) in HIV-infected subjects. In: Clinical Pharmacology and Therapeutics. 1995 ; Vol. 58, No. 1. pp. 44-53.
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