Persistent Pulmonary Hypertension of the Newborn - Mattel ...

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Increased PDE3 activity in resistance PA after birthPDE-3 3 Inhibitor -MilrinoneMilrinone ↓ PVR and PAP in:•experimental models•adults•neonates- post cardiacsurgeryMilrinone inhibits NE-induced constriction inresistance PA from 1dSB and 100% O 2+iNO lambsChen, 2009
Milrinone Improves Oxygenationin Neonates With SeverePPHN• Routes <strong>of</strong> administration reported - IV, inhalation• Potential AEs:• Hypotension, thrombocytopenia, intra-cranial bleedMcNamara, 2006, J Crit Care
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Page 9 and 10: Off Label Drug Use• FDA regulates
Page 11 and 12: Off Label Drug Use• New uses, dos
Page 13 and 14: Post-INO Era• Questionnaire to220
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Page 18: Regulation of Pulmonary Vascular To
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Page 27: PDE-3 3 Inhibitor - Milrinone• Pr
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Page 35: Regulation of Pulmonary Vascular To
Page 38 and 39: In utero exposure to PGSynthetase i
Page 40 and 41: Non-selective action:• Systemic &
Page 42 and 43: PGE 1 - Metabolism70-95%PGE 115-OH
Page 44 and 45: Studies of Inhaled Prostaglandins i
Page 46 and 47: Studies of Inhaled Prostaglandins i
Page 48 and 49: Phase I Clinical Trial of IPGE 1 in
Page 50 and 51: Phase I Trial: Dose ResponseDoseng/
Page 52 and 53: Phase I Trial: Adverse Effects:No e
Page 54 and 55: Effect on Ductus Arteriosus• Echo
Page 56 and 57: Stability and Emitted DoseModified
Page 58 and 59: ResultsLC-MS Chromatograms Followin
Page 60 and 61: Aerosol Particle Size DistributionA
Page 62 and 63: Pharmacokinetics of IPGE 1 ?
Page 64 and 65: Nominal DoseAerosolizedRemain in de
Page 66 and 67: Aerosol Delivery Assessed by MRIExp
Page 68 and 69: Aerosol Delivery Assessed by MRI450
Page 70 and 71: Aerosol Delivery During HFOVSood et
Page 72 and 73: Preliminary Data - Conclusions• P
Page 74 and 75: Specific AimsPrimary Aims:‣ Evalu
Page 76: Challenges: RCTs in PPHN• Small n
Page 79 and 80:
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