RT Journal Article
SR Electronic
T1 Pulmonary Delivery of Intratracheally Instilled and Aerosolized Cyclosporine A to Young and Adult Rats
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 917
OP 920
VO 25
IS 8
A1 Witold Taljanski
A1 Stefan G. Pierzynowski
A1 Pal D. P. Lundin
A1 Björn R. Weström
A1 Stefan Eirefelt
A1 Jerzy Podlesny
A1 Magnus Dahlbäck
A1 Henryka Siwinska-Golebiowska
A1 Börje W. Karlsson
YR 1997
UL http://dmd.aspetjournals.org/content/25/8/917.abstract
AB The delivery and pharmacokinetics of cyclosporine A (CyA) given locally to the airways or iv was evaluated in young and adult rats. After intratracheal (i.t.) instillation of saline suspended CyA to adult rats, the CyA plasma levels peaked at 30 min with a bioavailability of 78.1 ± 6.9%. After the i.t. instillation of CyA with micelles forming surfactant, Cremophor EL, in adult and young rats, the plasma levels peaked at 5 min with a bioavailability of 77.5 ± 7.2% and 66.3 ± 4.5%, respectively. The bioavailability of aerosolized CyA was 80.1 ± 4.1% in adults. Thus, CyA is absorbed by the lungs into the systemic circulation of the rat in high amounts, independent of age and type of delivery system. Long-term treatment with i.t. instillations did not affect body weight gain in young and adult rats, and no histopathological changes were found in the lungs. It is important to emphasize that CyA plasma clearance in young rats was lower and elimination half-life longer than in adults. The slow elimination of CyA in young rats indicated profound pharmacokinetic age differences for this species. The American Society for Pharmacology and Experimental Therapeutics