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.