BIOMAT Database Logo BIOMAT Database Logo

Safety and pharmacokinetics of 566C80, a hydroxynaphthoquinone with anti-Pneumocystis carinii activity: a phase I study in human immunodeficiency virus (HIV)-infected men. 1991

W T Hughes, and W Kennedy, and J L Shenep, and P M Flynn, and S V Hetherington, and G Fullen, and D J Lancaster, and D S Stein, and S Palte, and D Rosenbaum
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38101-0318.

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.

UI MeSH Term Description Entries
D008297 Male Males
D009285 Naphthoquinones Naphthalene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups. Naphthalenediones,Naphthazarins,Naphthoquinone
D011020 Pneumonia, Pneumocystis A pulmonary disease in humans occurring in immunodeficient or malnourished patients or infants, characterized by DYSPNEA, tachypnea, and HYPOXEMIA. Pneumocystis pneumonia is a frequently seen opportunistic infection in AIDS. It is caused by the fungus PNEUMOCYSTIS JIROVECII. The disease is also found in other MAMMALS where it is caused by related species of Pneumocystis. P carinii Pneumonia,P. carinii Pneumonia,P. jirovecii Pneumonia,PCP Pneumonia,Pneumocystis Pneumonia,Pneumocystosis,Pneumonia, Interstitial Plasma Cell,PCP Infection,Pneumocystis carinii Pneumonia,Pneumocystis jirovecii Pneumonia,Pneumonia, Pneumocystis carinii,Infection, PCP,P carinii Pneumonias,P. carinii Pneumonias,P. jirovecii Pneumonias,PCP Infections,PCP Pneumonias,Pneumocystis Pneumonias,Pneumocystoses,Pneumonia, P carinii,Pneumonia, P. carinii,Pneumonia, P. jirovecii,Pneumonia, PCP,Pneumonia, Pneumocystis jirovecii,Pneumonias, PCP
D004341 Drug Evaluation Any process by which toxicity, metabolism, absorption, elimination, preferred route of administration, safe dosage range, etc., for a drug or group of drugs is determined through clinical assessment in humans or veterinary animals. Evaluation Studies, Drug,Drug Evaluation Studies,Drug Evaluation Study,Drug Evaluations,Evaluation Study, Drug,Evaluation, Drug,Evaluations, Drug,Studies, Drug Evaluation,Study, Drug Evaluation
D004361 Drug Tolerance Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL. Drug Tolerances,Tolerance, Drug,Tolerances, Drug
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes
D006716 Homosexuality The sexual attraction or relationship between members of the same SEX. Homosexuality, Ego-Dystonic,Ego-Dystonic Homosexuality,Homosexuality, Ego Dystonic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000935 Antifungal Agents Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues. Anti-Fungal Agents,Antifungal Agent,Fungicides, Therapeutic,Antibiotics, Antifungal,Therapeutic Fungicides,Agent, Antifungal,Anti Fungal Agents,Antifungal Antibiotics

Related Publications

W T Hughes, and W Kennedy, and J L Shenep, and P M Flynn, and S V Hetherington, and G Fullen, and D J Lancaster, and D S Stein, and S Palte, and D Rosenbaum
Efficacy of a hydroxynaphthoquinone, 566C80, in experimental Pneumocystis carinii pneumonitis.
February 1990, Antimicrobial agents and chemotherapy,
W T Hughes, and W Kennedy, and J L Shenep, and P M Flynn, and S V Hetherington, and G Fullen, and D J Lancaster, and D S Stein, and S Palte, and D Rosenbaum
Pneumocystis carinii infection among human immunodeficiency virus (HIV) infected Myanmar patients.
September 2003, The Southeast Asian journal of tropical medicine and public health,
W T Hughes, and W Kennedy, and J L Shenep, and P M Flynn, and S V Hetherington, and G Fullen, and D J Lancaster, and D S Stein, and S Palte, and D Rosenbaum
Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients.
February 1990, Archives of internal medicine,
W T Hughes, and W Kennedy, and J L Shenep, and P M Flynn, and S V Hetherington, and G Fullen, and D J Lancaster, and D S Stein, and S Palte, and D Rosenbaum
Phase I dose escalation trial evaluating the pharmacokinetics, anti-human cytomegalovirus (HCMV) activity, and safety of 1263W94 in human immunodeficiency virus-infected men with asymptomatic HCMV shedding.
September 2002, Antimicrobial agents and chemotherapy,
W T Hughes, and W Kennedy, and J L Shenep, and P M Flynn, and S V Hetherington, and G Fullen, and D J Lancaster, and D S Stein, and S Palte, and D Rosenbaum
Preventing Pneumocystis carinii pneumonia in persons infected with human immunodeficiency virus.
August 1995, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America,
W T Hughes, and W Kennedy, and J L Shenep, and P M Flynn, and S V Hetherington, and G Fullen, and D J Lancaster, and D S Stein, and S Palte, and D Rosenbaum
Pneumocystis carinii pneumonia in human immunodeficiency virus-infected infants and children.
January 1993, Pharmacotherapy,
W T Hughes, and W Kennedy, and J L Shenep, and P M Flynn, and S V Hetherington, and G Fullen, and D J Lancaster, and D S Stein, and S Palte, and D Rosenbaum
Pharmacokinetics, safety and anti-human immunodeficiency virus (HIV) activity of hydroxyurea in combination with didanosine.
October 1998, The Journal of antimicrobial chemotherapy,
W T Hughes, and W Kennedy, and J L Shenep, and P M Flynn, and S V Hetherington, and G Fullen, and D J Lancaster, and D S Stein, and S Palte, and D Rosenbaum
Pneumocystis carinii pneumonia in South African children infected with human immunodeficiency virus.
July 2000, The Pediatric infectious disease journal,
W T Hughes, and W Kennedy, and J L Shenep, and P M Flynn, and S V Hetherington, and G Fullen, and D J Lancaster, and D S Stein, and S Palte, and D Rosenbaum
Prophylaxis for Pneumocystis carinii pneumonia in patients infected with human immunodeficiency virus.
May 1992, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America,
W T Hughes, and W Kennedy, and J L Shenep, and P M Flynn, and S V Hetherington, and G Fullen, and D J Lancaster, and D S Stein, and S Palte, and D Rosenbaum
Prophylaxis against Pneumocystis carinii pneumonia in children infected with human immunodeficiency virus.
April 1991, CDR (London, England : Weekly),
Copied contents to your clipboard!