Concentrations of aerosolized pentamidine in bronchoalveolar lavage, systemic absorption, and excretion.

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RESUMO

Pentamidine pulmonary pharmacokinetics were studied in 13 patients receiving once-daily inhaled therapy and 4 patients receiving low-dose intravenous treatment for Pneumocystis carinii pneumonia. Twenty-four hours after inhaled or intravenous therapy, the mean (+/- standard deviation) concentrations of pentamidine in serial bronchoalveolar specimen fluid ranged from 28.6 +/- 10 to 177.5 +/- 28 ng/ml and 6.05 +/- 2.29 to 21.4 +/- 15.7 ng/ml, respectively. Pentamidine concentrations in brochoalveolar fluid were generally higher after 2 weeks than after day 1 of therapy; however, the differences were not statistically different (P greater than 0.05). The pulmonary half-life after inhaled therapy is long; pentamidine was detectable in bronchoalveolar fluid at 33 (one patient), 69 (one patient), and 115 (one patient) days following the completion of 2 weeks of therapy. Systemic absorption of pentamidine was minimal; the mean (+/- standard deviation) plasma concentration at the completion of inhalation was 13.84 +/- 11.8 ng/ml, or 5% of the mean peak plasma concentration achieved after intravenous administration. Accumulation in the plasma did not occur with repeated inhalation as has been described with multiple intravenous dosing. Cumulative urinary excretion 24 h after the first dose was 5% of that observed with intravenous administration. These data may have importance in designing dosage regimens for the further investigation of inhaled pentamidine for treatment or prophylaxis of P. carinii pneumonia.

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