Balance/excretion of ³H- and ¹⁴C-tyloxapol in the male rabbit after intratracheal administration

Abstract

1. Tyloxapol, trace-labelled (50–100 μCi/animal) with ³H or ¹⁴C, was administered intratracheally in a surfactant formulation (EXOSURF Neonatal) to the male rabbit in a total tyloxapol dose of 5 mg/kg. Urine, faeces, expired air, and blood were collected for up to 10 days following tyloxapol administration.

2. Over 5 days, ³H-tyloxapol-related radioactivity in the urine (13 ± 4%) and faeces (27 ± 4%) accounted for a major fraction of the labelled dose. However, urine also contained an additional 13% of the dose as tritiated water. Expired air accounted for only 4 ± 2% of the dose. At the end of the study, an additional 35 ± 6% of the radioactive dose was found in tissues and the carcass, mainly in the lung (27 ± 4%) and to a lesser extent in the liver (2 ± 8%) and kidney (0 ± 4%). Levels of radioactivity in other tissues, including whole blood, were low.

3. Over a separate 10-day study, faecal (30 ± 4%) and renal (9 ± 7%) elimination of ¹⁴C-tyloxapol accounted for 40% of the radioactive dose, with expired air accounting for much less (2 ± 7%). At the end of the study, additional radioactivity was recovered from the lung (43 ± 9%) and to a lesser extent from the liver (3 ± 8%) and kidney (0 ± 3%). The half-life for the elimination of total radioactivity from the lung was estimated to be 10–12 days.

4. These data indicate that, following intratracheal administration, tyloxapol and metabolites were retained by the lung, released slowly into the systemic circulation, and eliminated through faecal and renal excretion.