US EPA

979024 

Journal Article 

Tissue Distribution, Metabolism and Excretion of PGE(1) Following Prolonged High-Dose Inhalation in Neonatal Pigs 

Sood, BG; Chen, X; Dawe, EJ; Malian, M; Maddipati, KR 

2010 

Yes 

International Journal of Pharmacology
ISSN: 1811-7775 

6 

3 

224-230 

English 

WOS:000285675700008 

Inhaled prostaglandin E(1)(IPGE(1)) is a potential selective pulmonary vasodilator in neonatal pulmonary hypertension. The objective of this study was to evaluate the bioavailability and metabolism of IPGE(1). Anesthetized ventilated piglets received either high dose IPGE(1) (1200 ng/kg/min) [Study group] or nebulized saline [Control group] using a jet nebulizer. PGE(1) and its metabolite, 15-keto-PGE(1), were quantified in blood, urine and lung tissue using high performance liquid chromatography-mass spectrometry. Fourteen piglets underwent the experimental protocol (age 1-9 days). Of these, nine received IPGE(1) and five received nebulized saline. Among control pigs, two died of complications at 3-4 h, one at 12-13 h and the remaining two were euthanized at 24 h after start of aerosol. In the study group, three animals died after 14-15 h of aerosol treatment of iatrogenic complications and six animals received aerosol for 24 h. Plasma and urine PGE(1) levels increased significantly over time in study (p<0.05) but not control animals. Plasma and urinary 15-keto-PGE(1) levels and lung tissue prostaglandin profile were comparable in study and control animals. In conclusion, this is the first report of the tissue distribution, metabolism and excretion of prolonged high dose IPGE(1). The increase in PGE(1) levels in plasma and urine over time without accumulation in lung tissue or systemic side effects suggests effective aerosol delivery, extensive pulmonary metabolism and efficient excretory mechanisms. 

Neonatal hypoxemic respiratory failure; persistent pulmonary hypertension of the newborn; aerosolized; selective pulmonary vasodilator; prostaglandin E-1/alprostadil; newborn