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Antimicrobial Agents and Chemotherapy, July 1998, p. 1597-1600, Vol. 42, No. 7
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Pharmacokinetic Evaluation of Amphotericin B in Lung Tissue: Lung Lymph Distribution after Intravenous Injection and Airspace Distribution after Aerosolization and Inhalation of Amphotericin B

Tomonobu Koizumi, Keishi Kubo,* Toshimichi Kaneki, Masayuki Hanaoka, Toshihide Hayano, Takayuki Miyahara, Kazuyoshi Okada, Keisaku Fujimoto, Hiroshi Yamamoto, Toshio Kobayashi, and Morie Sekiguchi

First Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1 Asahi Matsumoto, 390-8621 Japan

Received 18 August 1997/Returned for modification 31 January 1998/Accepted 27 April 1998

We have studied the pharmacokinetics of amphotericin B (AmB) in lung lymph circulation and bronchial-wash fluid after intravenous infusion and inhalation, respectively. For two experiments with awake sheep, we used lung lymph fistulas and tracheotomy. In experiment 1, AmB concentrations in plasma and lung lymph after intravenous infusion of AmB (1 mg/kg of body weight) over 1.5 h were measured. The mean peak in plasma level was 756.0 ± 188.8 ng/ml at 3 h after the start of infusion, and the level then decreased gradually to 194.8 ± 28.9 ng/ml at 24 h. The stable and maximal levels in lung lymph last 5 to 9 h after the start of AmB infusion. The concentrations in lung lymph after 9 h were slightly higher than those in plasma. Thus, the lung lymph-to-plasma ratio of AmB concentrations increased gradually during infusion, and the ratio was more than 1.0 after the end of infusion, suggesting that AmB could be easily moved from plasma to pulmonary interstitium and/or lung lymph circulation. In another experiment, 5 or 30 mg of aerosol AmB was inhaled, and the concentration of AmB in the bronchial-wash fluid was determined by bronchoalveolar lavage. The peak AmB concentration in the fluid was observed at 0.5 h. After that, AmB was slowly eliminated over 24 h. The area under the concentration-time curve for 30 mg of inhaled AmB was higher than that for 5 mg, but maximum concentrations of AmB in serum for 5 and 30 mg were almost similar. These observations identify the pharmacokinetic characteristics of AmB in the lung and may provide a new insight into the strategy for clinical treatment of fungal pneumonia.

* Corresponding author. Mailing address: First Department of Internal Medicine, Shinshu University of Medicine, 3-1-1 Asahi Matsumoto, 390-8621 Japan. Phone: 263-35-4600, ext. 5252. Fax: 263-36-3722.

Antimicrobial Agents and Chemotherapy, July 1998, p. 1597-1600, Vol. 42, No. 7
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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