Safety and pharmacokinetics of 566C80, a hydroxynaphthoquinone with anti-Pneumocystis carinii activity: a phase I study in human immunodeficiency virus (HIV)-infected men.
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 micrograms/ml; time to maximum plasma concentration, 8.0 h; area under plasma concentration-time curve at steady state, 1088 h.micrograms/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.
Hughes
W T
WT
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38101-0318.
Kennedy
W
W
Shenep
J L
JL
Flynn
P M
PM
Hetherington
S V
SV
Fullen
G
G
Lancaster
D J
DJ
Stein
D S
DS
Palte
S
S
Rosenbaum
D
D
D000328:Adult; D000935:Antifungal Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D053626:Atovaquone; D015331:Cohort Studies; D004341:Drug Evaluation; D004361:Drug Tolerance; D015658:HIV Infections / Q000150:complications*; D006207:Half-Life; D006716:Homosexuality; D006801:Humans; D008297:Male; D009285:Naphthoquinones / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy / Q000517:prevention & control*
D000935:Antifungal Agents; D009285:Naphthoquinones; D053626:Atovaquone