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Serial pentamidine levels in bronchial epithelial lining fluid after aerosol administration
H Yamamoto1, T Koizumi, T Miyahara
1First Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Background:
There is no information on serial pharmacokinetic assessment in the lungs after administration of aerosolized pentamidine.
Objective:
The present study was performed to evaluate the elimination of aerosolized pentamidine from bronchial airways following inhalation.
Methods:
We used 4 sheep with tracheotomies in the present study. Pentamidine (300 mg) was administered by inhalation to each animal. Serial bronchial washing to obtain epithelial lining fluid (ELF) was performed 1, 7, 10, 14, 21 and 28 days after administration of aerosolized pentamidine in each animal. The pentamidine concentration in the supernatant of ELF was measured by high-performance liquid chromatography.
Results:
The maximal pentamidine level on the first day (12 h after inhalation) was 616.5 +/- 238.2 ng/ml (mean +/- SE) in ELF. The pentamidine levels rapidly decreased within 2 weeks (8.9 +/- 1.2 ng/ml at 14 days), followed by slow elimination (8.9 +/- 0.8 ng/ml at 28 days). Thus, inhaled pentamidine showed a rapid clearance from the bronchial wall within the first 2 weeks.
Conclusions:
These findings may be useful in designing and interpreting future studies of aerosolized pentamidine in patients who are receiving inhaled pentamidine, especially for those with failure of prophylaxis for Pneumocystis carinii pneumonia.