Entry of five antifungal agents into the ovine lung

The passage of antifungal agents into pulmonary parenchyma was studied in normal sheep prepared by cannulation of the right external jugular vein and the efferent duct of the right caudal mediastinal lymph node. Five sheep were given single, sequential, intravenous injections of flucytosine, ketoconazole, BAY n 7133, amphotericin B methyl ester, and amphotericin B. Venous blood plasma and pulmonary lymph were collected before infusion and from 5 min to 24 h postinfusion; the concentrations of the drugs were assayed by a well-agar diffusion method. All drugs appeared promptly in the pulmonary lymph and disappeared at approximately exponential rates from both liquids. The lymph/plasma ratios of the drug concentrations did not differ between flucytosine and the two azoles but were lower for both polyenes. Binding by plasma proteins did not appear to be a determinant of pulmonary entry.