Persistent Pulmonary Hypertension of the Newborn - Mattel ...

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Effect on Ductus Arteriosus• Echocardiograms obtained before andafter study in 5 animals• High dose IPGE 1for 24 hrs did notopen a functionally closed DA• In one animal with small DA,administration of IPGE 1did not changethe size of the DATable 3: Morphometry of the DA at AutopsyControl(n=6)IPGE 1(n=9)Length 0.47 (0.05) 0.49 (0.06)Circumference (Aortic) 0.33 (0.08) 0.34 (0.09)Circumference (Pulmonary) 0.33 (0.08) 0.33 (0.11)Values represent mean (SD) in mm. Group differences not significantControlIPGE 1Gittenberger-de Groot, 1980Sood et al, POLM, 2009
Is IPGE 1 Stable Upon Aerosolization?What is the Emitted Dose?What is the APSD?
Page 7 and 8: It is 4 AM in the morning -------Yo
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
Page 16 and 17: Regulation of Pulmonary Vascular To
Page 18: Regulation of Pulmonary Vascular To
Page 21 and 22: PO Sildenafil• 1 st dose - 1 mg/0
Page 23 and 24: PDE-5 5 Inhibitor - Sildenafil• R
Page 25 and 26: PDE-5 5 Inhibitor - Sildenafil• P
Page 27 and 28: PDE-3 3 Inhibitor - Milrinone• Pr
Page 29 and 30: Milrinone Improves Oxygenationin Ne
Page 31 and 32: Regulation of Pulmonary Vascular To
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 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: Thank YouDiscussion

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