Phase 1 study of combination therapy with L-697,661 and zidovudine

Robert T. Schooley*, Thomas B. Campbell, Daniel R. Kuritzkes, Terrence Blaschke, Daniel S. Stein, Mary E. Rosandich, John Phair, John C. Pottage, Ferdinand Messari, Ann Collier, James Kahn

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

We performed a pilot study that examined the clinical and pharmacokinetic interactions between zidovudine (ZDV) and a pyridinone derivative, L-697-661. The results indicate that the drugs were well tolerated, with no important pharmacokinetic interactions, when administered concomitantly for as long as 8 weeks. Although the number of study participants was small, we noted rapid emergence of resistance to L-697,661 among ZDV-naive study subjects who were administered L-697,661 as monotherapy but did not observe isolates of human immunodeficiency virus type 1 (HIV-1) resistant to L-697,661 among those who were administered concomitant ZDV. These results suggest a potential interaction between development of resistance to L-697,661 and ZDV. Although the clinical development of L- 697,661 has been halted, our results support the need for further studies to test whether specific interactions among antiretroviral agents administered in combination and the molecular target can delay the emergence of isolates that exhibit resistance to all drugs in the regimen.

Original languageEnglish (US)
Pages (from-to)363-370
Number of pages8
JournalJournal of Acquired Immune Deficiency Syndromes and Human Retrovirology
Volume12
Issue number4
DOIs
StatePublished - 1996

Keywords

  • Combination therapy
  • Human immunodeficiency virus-1
  • L- 697,661
  • Pharmacokinetic interactions
  • Zidovudine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Virology

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