Effects of aerosolized synthetic surfactant, atovaquone, and the combination of these on murine Pneumocystis carinii pneumonia.
An immunosuppressed rat model was used to determine the pharmacokinetics of aerosolized atovaquone (administered with and without a synthetic surfactant) and to evaluate the efficacy of inhaled atovaquone in the prevention and treatment of Pneumocystis carinii pneumonia (PCP). After a single dose by aerosol, mean peak concentrations of atovaquone averaged 52 microg/mL in plasma and 31 microg/g in lungs of rats infected with P. carinii. When atovaquone was combined with surfactant, mean peak concentrations of 94 microg/mL in plasma and 51 microg/g in lung were achieved. Aerosolized synthetic surfactant alone significantly increased survival of rats with PCP and, when combined with atovaquone, increased plasma and lung concentrations of the drug and eradication of the organism.
Hughes
W T
WT
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. walter.hughes@stjude.org
Sillos
E M
EM
LaFon
S
S
Rogers
M
M
Woolley
J L
JL
Davis
C
C
Studenberg
S
S
Pattishall
E
E
Freeze
T
T
Snyder
G
G
Staton
S
S
D000280:Administration, Inhalation; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology; D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D053626:Atovaquone; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology; D004359:Drug Therapy, Combination; D008168:Lung / Q000737:chemistry / Q000382:microbiology; D008297:Male; D009285:Naphthoquinones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy* / Q000517:prevention & control*; D011663:Pulmonary Surfactants / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000494:pharmacology
D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D000935:Antifungal Agents; D009285:Naphthoquinones; D011663:Pulmonary Surfactants; D003907:Dexamethasone; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D053626:Atovaquone