Relationship between plasma concentrations of 3‘-deoxy-3’-fluorothymidine (alovudine) and antiretroviral activity in two concentration-controlled trials

Charles Flexner, Charles Van Der Horst, Mark A. Jacobson, William Powderly, Frederick Duncanson, Derek Ganes, Patricia A. Barditch-Crovo, Brent G. Petty, Penny A. Baron, Donald Armstrong, Patricia Bricmont, Olatunde Kuye, Avraham Yacobi, Robert Desjardins, Bruce Polsky

Research output: Contribution to journalArticlepeer-review

Abstract

Two concentration-controlled trials (CCTs) defined the relationship between plasma concentrations of 3‘-deoxy-3’-fluorothymidine (alovudine) and changes in surrogate markers of antiretroviral activity. In an initial open-label CCT involving 14 subjects infected with human immunodeficiency virus (HIV), unacceptable hematologic toxicity occurred when the area under the concentration-time curve during a 12-h dosing interval (AUC12) was ���� 300 ng*h/mL. Consequently, 46 subjects were assigned to AUC12 s of 50, 100, or 200 ng*h/mL for up to 16 weeks in a prospective, randomized, double-blind CCT. Alovudine caused a concentration-dependent reduction in p24 antigen and peripheral blood mononuclear cell HIV titers within 4 weeks of start of treatment. The AUC12 producing a 50% reduction in p24 (108 ng*h/mL) had a trough concentration identical to the reported IC50 of alovudine in HIV-infected H9 cells. It may be possible to predict the antiretroviral activity of certain nucleoside analogues as a function of plasma drug concentration.

Original languageEnglish (US)
Pages (from-to)1394-1403
Number of pages10
JournalJournal of Infectious Diseases
Volume170
Issue number6
DOIs
StatePublished - Dec 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Relationship between plasma concentrations of 3‘-deoxy-3’-fluorothymidine (alovudine) and antiretroviral activity in two concentration-controlled trials'. Together they form a unique fingerprint.

Cite this