Intratracheal administration of glucocorticoids using surfactant as a vehicle.
1. Glucocorticoids are an effective treatment in the amelioration of chronic lung disease in neonates. However, systemic administration of glucocorticoids to neonates is associated with significant side-effects that preclude them as an early intervention to prevent onset of the condition. Conversely, local intratracheal administration of glucocorticoids may prevent inflammatory insult to the lungs without the development of systemic side-effects. We therefore investigated whether local intratracheal delivery of corticosteroids could be facilitated using surfactant as a vehicle. 2. Addition of dexamethasone to either diluted or commercial artificial surfactant, Survanta (Abbott Industries, Sydney, NSW, Australia), did not alter the surface properties of the surfactant. 3. After intratracheal instillation to rats, radiolabelled dexamethasone in Survanta was well distributed throughout all four lobes of the lungs. A concentration gradient of the steroid was observed between the root and the peripheral sections of all lobes. 4. Our results suggest that surfactant is an effective vehicle for intratracheal delivery of glucocorticoids. Moreover, we propose that prophylactic intratracheal administration of glucocorticoids administered shortly after birth may prevent inflammatory insult to the lungs and thereby reduce the likelihood of chronic lung disease developing.
Nimmo
Alan J
AJ
Department of Physiology and Pharmacology, James Cook University, South Australia, Australia. Alan.Nimmo@jcu.edu.au
Carstairs
Jill R
JR
Patole
Sanjay K
SK
Whitehall
John
J
Davidson
Kate
K
Vink
Robert
R
D000818:Animals; D001688:Biological Products; D003907:Dexamethasone / Q000008:administration & dosage / Q000493:pharmacokinetics; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008171:Lung Diseases / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D014677:Pharmaceutical Vehicles; D011663:Pulmonary Surfactants / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013501:Surface-Active Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics
D001688:Biological Products; D005938:Glucocorticoids; D014677:Pharmaceutical Vehicles; D011663:Pulmonary Surfactants; D013501:Surface-Active Agents; D003907:Dexamethasone; C072197:beractant