Pulmonary absorption of carboxyfluorescein in the rat

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Abstract
The pulmonary absorption of the fluorescent marker 6‐carboxyfluorescein (CF) has been characterized. CF was administered intratracheally (i.t.) as a fluid instillate to pentobarbitone‐anaesthetized rats at doses of 0.5 and 2 mg kg−1. The absorption was characterized by both model‐independent and model‐dependent pharmacokinetic analyses of blood concentration data with reference to previous intravenous (i.v.) studies. The mean fraction available (F) of CF was 90 and 112% with a mean absorption time of 107 and 109 min for the lower and higher doses, respectively. The terminal half‐life for the i.t. administered CF (73 and 83 min for the 0.5 and 2 mg kg−1 doses, respectively) was significantly longer (P < 0.001) than after i.v. dosing (18 min). This indicates a slow pulmonary absorption of CF. Blood concentration‐time profiles could not be adequately described by models involving a simple first‐order absorption process; a model incorporating two simultaneous first‐order inputs gave a much better description, its absorption rate constants differing by almost two orders of magnitude.