A Study of Two Forms of Pentamidine in HIV-Infected Children Who May Have Pneumocystis Carinii Pneumonia
Condition: Pneumonia, Pneumocystis Carinii; HIV Infections
MeSH terms: Infections; Pneumonia; HIV Infections; Acquired Immunodeficiency Syndrome; Pneumonia, Pneumocystis
Study type: Interventional
Phase: Phase 1

Summary: 
      To evaluate the delivery of a single dose of aerosolized pentamidine to children; to evaluate
      the tolerance of pentamidine administration by mask; to compare intravenous pentamidine first
      dose pharmacokinetics (blood levels) in children with information previously collected on
      adults; and to compare plasma pentamidine levels in children after an aerosolized treatment
      with levels previously collected on adults.

      Pneumocystis carinii pneumonia (PCP) is the most common serious infection in children with
      AIDS and is associated with a high death rate. Current approved treatment includes
      intravenous trimethoprim - sulfamethoxazole (TMP / SMX) and intravenous pentamidine, which
      are both effective in treatment of the first episode of PCP pneumonia. However, both
      therapies have a 50 percent or greater incidence of adverse reactions. Because of serious
      toxicities, drug treatment has had to be discontinued. Animal studies show that aerosolized
      pentamidine (pentamidine given through inhalation) is as effective as intravenous
      pentamidine. It is hoped that the aerosolized route will be less toxic than intravenous
      pentamidine. The study is the first step in evaluating the delivery of aerosolized
      pentamidine to children.
    

Detailed description: 
      Pneumocystis carinii pneumonia (PCP) is the most common serious infection in children with
      AIDS and is associated with a high death rate. Current approved treatment includes
      intravenous trimethoprim - sulfamethoxazole (TMP / SMX) and intravenous pentamidine, which
      are both effective in treatment of the first episode of PCP pneumonia. However, both
      therapies have a 50 percent or greater incidence of adverse reactions. Because of serious
      toxicities, drug treatment has had to be discontinued. Animal studies show that aerosolized
      pentamidine (pentamidine given through inhalation) is as effective as intravenous
      pentamidine. It is hoped that the aerosolized route will be less toxic than intravenous
      pentamidine. The study is the first step in evaluating the delivery of aerosolized
      pentamidine to children.

      Sixteen patients are assigned into one of the following groups. Group 1 (four patients)
      receives intravenous pentamidine as a one-time dose, infused over 2 hours. Group 2a (six
      patients) receives aerosolized pentamidine via face mask. Group 2b (six patients) receives
      aerosolized pentamidine 2 times. Group 2b will be studied only if initial dose is well
      tolerated. Small amounts (1 - 2 cubic centimeters) of blood is taken from all groups at 40
      minutes, and 2, 3, 7, 14, and 24 hours from the beginning of pentamidine treatment and at the
      same time as the lung biopsy or bronchial alveolar lavage. Patients are given routine TMP /
      SMX (or whatever medications are considered appropriate by the patient's primary physician
      for medical management) dosing 1 - 2 hours after pentamidine is given. Bronchial alveolar
      lavage fluid or lung tissue from biopsy will be obtained between 2 - 48 hours after
      initiation of pentamidine treatment (optionally 10 - 24 hours post dose).
    

Intervention name(s): Pentamidine isethionate
Intervention type(s): Drug
Intervention MeSH terms: Pentamidine
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: AIDS-Related Opportunistic Infections; Pneumonia, Pneumocystis carinii; Pentamidine; Injections, Intravenous; Drug Evaluation; Aerosols; Acquired Immunodeficiency Syndrome