Phase I/II study of the toxicity, pharmacokinetics, and activity of the HIV protease inhibitor SC-52151

Margaret A. Fischl, Douglas D. Richman, Charles Flexner, Michael F. Para, Richard Haubrich, Aziz Karim, Patrick Yeramian, Jeanne Holden-Wiltse, Patricia M. Meehan

Research output: Contribution to journalArticlepeer-review

Abstract

SC-52151, an HIV- 1 protease inhibitor, was developed as an ethanol- based elixir and subsequently as a self-emulsifying drug delivery system (SEDDS) to improve bioavailability. To evaluate formulation and treatment regimen effects, we conducted a four-arm, phase I/II study using the highest previously tested daily dose, 2250 mg. Forty-nine patients received the elixir or SEDDS at a dosage of 750 mg three times daily or 1125 mg twice daily for 14 days. One patient developed hypertriglyceridemia, and one had fever and dyspnea. The SEDDS formulation compared with the elixir resulted in a larger area under the concentration-time curve (AUC, p < 0.001), peak (Cmax, p = 0.041) and trough (Cmin, p = 0.025). Twice-daily administration compared with administration three times daily produced a higher cumulative AUC (p = 0.008). Both SEDDS regimens produced mean plasma concentrations above the 90% inhibitory concentration (IC90) for HIV. A mean decline of 0.03 log10 RNA copies (SEDDS) and an increase of 0.15 log10 (elixir) were observed. Although SC-52151 was well federated and the SEDDS formulation resulted in plasma concentrations above the [C90 for viral replication, no antiviral activity was produced.

Original languageEnglish (US)
Pages (from-to)28-34
Number of pages7
JournalJournal of Acquired Immune Deficiency Syndromes and Human Retrovirology
Volume15
Issue number1
DOIs
StatePublished - May 1 1997

Keywords

  • Antiretroviral therapy
  • HIV-1 protease inhibitor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Virology

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