336 - The Efficacy of Surfactant (curosurf) as Vehicle for Budesonide Delivery to the Lung.

Publication Number: 1320.336

TsuFuh Yeh, Taipei Medical University, Irvine, CA, United States; Kang Wei Chang, Taipei Medical University, Taipei, Taipei, Taiwan (Republic of China); Chih Hsueh Lin, Hungkuang University, Taichung, Taichung, Taiwan (Republic of China); Ming-Chih Lin, National Chung Hsing University, Taichung, Taichung, Taiwan (Republic of China); Chung-Ming Chen, Taipei Medical Univesity Hospital, Taipei, Taipei, Taiwan (Republic of China); Mei Hui Wang, National Atomic Research Institute, Taoyuan City, Taoyuan, Taiwan (Republic of China)

Background: BPD is the most serious complication in preterm with RDS with high mortality and morbidity. Recent studies indicated that endotracheal budesonide using surfactant as vehicle significantly reduced the incidence of BPD and severity of BPD. However, the results from many randomized trials were inconsistent in efficacy. The reason for this inconsistency is not clear. There are two factors that may affect the efficacy of budesonide delivery: 1) patency of the airway 2) sustained surface tension gradient between the proximal and distal airway. Ventilation induced lung injury (VILI) occurs very early, potentially in hours. VILI will lead to edema and high viscosity, leading to airway obstruction. We therefore hypothesized that, to be effective for budesonide delivery, budesonide/surfactant (B/S) should be given as early as possible before VILI occurs. An animal experiment using isotope (F-18) labeled budesonide/surfactant (curosurf) was done and the budesonide radioactivity was measured by a PET scan.

Objective: To evaluate the time of intervention (intratracheal B/S) and the effect of budesonide delivery to the lung.

Design/Methods: Four male adult rats were anesthetized and ventilated. RDS model was established by repeated saline lavage through tracheostomy tube. Four studies (four rats) were done using isotope labelled budesonide:
1) Budesonide/curosurf without prior ventilation (IMV).
2) Budesonide/curosurf after 6 hours of IMV (VT 8 ml/kg, FiO2 0.6).
3) Budesonide/curosurf after 6 hours of IMV and with LPS insult (VT 8 ml/kg, FiO2 0.6).
4) Budesonide/curosurf after 12 hours of IMV (VT 8 ml/kg, FiO2 0.6).

Results: Figure 1 showed the radioactivity or budesonide distribution in lung in rat with budesonide alone or with budesonide/surfactant. It is clear that with the use of budesonide/surfactant (curosurf), budesonide can be easily delivered to lung.
Figure 2 showed that immediately after intratracheal administration of isotope labeled budesonide/surfactant (curosurf) without prior IMV.
Figure 3 showed that after ventilation (VT 8 ml/kg, FiO2 0.6) for 6 hours, with or without LPS, and also 12 hours, budesonide delivery to lung was very low.

Conclusion(s): Intratracheal B/S was administered to rat who has been on IMV for 6-12 hours. Budesonide radioactivity was rarely detected in the lung. Therefore, for effective budesonide delivery using surfactant as vehicle, B/S should be given as early as possible. Budesonide may be considered as an adjunct to early surfactant therapy. For effective therapy of this therapeutic regimen, timing is everything. (Supported by Chiesi Farmaceutici S.p.A)

Budesonide distribution in lung in rat with budesonide alone or with budesonide/surfactant.


Budesonide distribution in lung in rat with budesonide/surfactant administration without prior IMV.


Budesonide distribution in lung in rat with budesonide/surfactant administration following 6-12 hours of IMV.