Pulmonary absorption of carboxyfluorescein in the rat.
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 less than 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.
Woolfrey
S G
SG
Taylor
G
G
Kellaway
I W
IW
Smith
A
A
D000042:Absorption; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005452:Fluoresceins / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D006207:Half-Life; D007442:Intubation, Intratracheal; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D051381:Rats; D011919:Rats, Inbred Strains
D005452:Fluoresceins; C024098:6-carboxyfluorescein