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

Abstract

1. Tyloxapol, trace-labelled (50-100 microCi/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.