Solute disposition in the rat lung in vivo and in vitro: Determining regional absorption kinetics in the presence of mucociliary escalator

✍ Scribed by Masahiro Sakagami; Peter R. Byron; Jurgen Venitz; Frantisek Rypacek

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 155 KB
• Volume: 91
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.10069

✦ Synopsis

Solute absorption from the airways was compared and modeled in vivo and in vitro isolated perfused rat lung (IPRL), and its regional kinetic descriptors in the presence of competing mucociliary escalator were estimated. 7.4 kDa ¯uorophorelabeled polyhydroxyethylaspartamide (F-PHEA), FITC-labeled dextran 40 (FD-4) and sodium ¯uorescein (F-Na) were used as model solutes. They were reproducibly administered into the airways in a range of doses in vivo and in vitro IPRL, and their initial deposition and subsequent absorption pro®les compared. Each of the absorption data was ®tted across doses to a kinetic model in which rate constants for Michaelis-Mententype active (V max,P and K m,P ) and/or ®rst-order passive (k a,P ) absorption and mucociliary escalator (k E ) were estimated simultaneously. Statistically indistinguishable initial solute distribution was ensured in vivo and in vitro. The absorption pro®les for F-PHEA were kinetically identical in vivo and in vitro, and their modeling analysis revealed the presence of competing, solute-independent pulmonary-to-bronchial mucociliary escalator with a half-life of 28.9 min. F-PHEA's active absorption was found to be 77 times faster than its passive absorption, yet this was present only in the pulmonary region. Passive solute absorption was inversely related to solute molecular weight [F-PHEA < FD-4 < F-Na]. Bronchial absorption was shown for F-Na in vivo and its rate indistinguishable from that from the pulmonary region. Thus, a single kinetic model was developed, enabling regional absorption kinetic analysis both in vivo and in vitro, in the presence of competing, solute-independent mucociliary escalator. ß 2002