Oral delivery of sodium cromolyn: preliminary studies in vivo and in vitro.
OBJECTIVE
Herein we report the discovery of a group of derivatized alpha-amino acids that increase the oral bioavailability of sodium cromolyn.


METHODS
We prepared three N-acylated alpha-amino acids and used these compounds to demonstrate the oral delivery of cromolyn in an in vivo rat model. In vitro experiments, including permeation studies and near infrared spectroscopy, were also performed to initiate an understanding of the mechanism by which these compounds facilitate cromolyn oral delivery.


RESULTS
Following oral administration to rats of solutions containing a combination of cromolyn and the delivery agent, significant systemic plasma concentrations of the drug were detected. In vitro studies suggest that absorption of the drug across the gastrointestinal membrane is a passive process.


CONCLUSIONS
The absolute oral bioavailability of sodium cromolyn in the rat model is estimated to be approximately 5%. Preliminary mechanistic studies suggest that a complex of the cromolyn/delivery agent facilitates permeation across/through the membrane.
Leone-Bay
A
A
Emisphere Technologies, Inc., Hawthorne, New York 10532, USA.
Leipold
H
H
Sarubbi
D
D
Variano
B
B
Rivera
T
T
Baughman
R A
RA
D000284:Administration, Oral; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001682:Biological Availability; D004205:Cromolyn Sodium / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D018927:Anti-Asthmatic Agents; D004205:Cromolyn Sodium