Safety and Pharmacokinetics of 566C80, a Hydroxynaphthoquinone with Anti-Pneumocystis carinii Activity: A Phase I Study in Human Immunodeficiency Virus (HIV)-Infected Men

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, fivecohorts of four human immunodeficiency virus-infected men received 100, 250, 750, 1500, and 3000mg of the compound orally once daily for 12 days. A sixth cohort received750mg 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; #x00B5;g/ml; plasma half-life, 51 h; and total plasma clearance, 4.09 lIh. Compound 566C80 offers promise as a new drug class for P. carinii pneumonia.