Comparison of tissular disposition of pentamidine mesylate in the rat after aerosol or parenteral administration.
The tissular distribution of pentamidine mesylate (4 mg/kg as free base) after intravenous, intramuscular, and aerosol administration in healthy rats was examined. Pentamidine levels in the plasma, lungs, liver, kidneys, and other organs were determined by high-performance liquid chromatography. Pentamidine was undetectable in the plasma after day 5. At day 1, the injected groups had high concentrations of the drug in the kidneys (32-34 micrograms/g) and spleen with much lower concentrations in the lungs and the liver (3.12-5.70 micrograms/g and 1.64-2.19 micrograms/g, respectively). Aerosol delivery of pentamidine produced negligible extrapulmonary drug levels (3.29 micrograms/g in kidneys at day 1) and high sustained pulmonary levels throughout the 60 d of the study (range 5.42-19.62 micrograms/g). The half-time of elimination was longer in the lungs and kidneys (29-45 d) than in the liver (1.4-7.0 d) regardless of the mode of administration.
Institut National de la Santé et de la Recherche Médicale, Unité 13, Centre Hospitalier Universitaire Bichat-Claude Bernard, Paris, France.
R
R
Farinotti
M B
MB
Pascaud
P M
PM
Girard
E
E
Guillot
A
A
Certain
J H
JH
Trouvin
D000336:Aerosols; D000578:Amidines / Q000493:pharmacokinetics*; D000818:Animals; D000981:Antiprotozoal Agents / Q000493:pharmacokinetics*; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008297:Male; D010419:Pentamidine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D000336:Aerosols; D000578:Amidines; D000981:Antiprotozoal Agents; D010419:Pentamidine