Safety and pharmacokinetics of 566C80, a hydroxynaphthoquinone with anti-pneumocystis carinii activity: A phase I study in human immunodeficiency virus (HIV)-infected men

W. T. Hughes, W. Kennedy, J. L. Shenep, P. M. Flynn, S. V. Hetherington, G. Fullen, D. J. Lancaster, D. S. Stein, S. Palte, D. Rosenbaum, S. H.T. Liao, M. R. Blum, M. D. Rogers

Research output: Contribution to journalArticlepeer-review

Abstract

A hydroxynaphthoquinone compound (566C80) has been shown to be effective in the prevention and treatment of murine Pneumocystis carinii pneumonitis. In a phase I study, five cohorts of four human immunodeficiency virus-infected men received 100, 250, 750, 1500, and 3000 mg of the compound orally once daily for 12 days. A sixth cohort received 750 mg three times daily for 5 days, then twice daily for 16 days. Evaluation included clinical, hematologic, and biochemical studies and the pharmacokinetics of 566C80. The only drug-related adverse effect was a maculopapular rash in one patient that resolved without discontinuation of the drug. With the largest dosage tested (3000 mg) the following pharmacokinetic measures were achieved: maximum plasma concentration, 39 μg/ml; time to maximum plasma concentration, 8.0 h; area under plasma concentration-time curve at steady state, 1088 h·μg/ml; plasma half-life, 51 h; and total plasma clearance, 4.09 l/h. Compound 566C80 offers promise as a new drug class for P. carinii pneumonia.

Original languageEnglish (US)
Pages (from-to)843-848
Number of pages6
JournalJournal of Infectious Diseases
Volume163
Issue number4
DOIs
StatePublished - 1991

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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