Abstract

Despite advances in antibiotic therapy and supportive care, chronic pulmonary infection with Pseudomonas aeruginosa continues to be the major cause of morbidity and mortality in cystic fibrosis. The host response to this infection is characterized by presistent infiltratin of neutrophils (PMNs), but these cells fail to eradicate the infection and may actually cause significant tissue damage. An excessive burden of uninhibitedelastase from PMNs is one of the proposed mechanisms whereby PMNs contribute to lung injury in CF. This project proposes to evaluate an potent protease inhibitor, DMP-777, for potential use in the treatment of CF lung disease.
The specific aims are (1) to evaluate the safety and tolerability of multiple doses of DMP-777, (2) to determine the pharmacokinetic and pharmacodynamic characteristics of multiple oral doses, and (3) to define the DMP-777 dosage level necessary to achieve sustained high-level systemic neutrophil elastase inhibition.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000080-36
Application #
6276558
Study Section
Project Start
1997-12-01
Project End
1998-11-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
36
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Case Western Reserve University
Department
Type
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106

  Publications

Randis, Tara M; Rice, Madeline Murguia; Myatt, Leslie et al. (2018) Incidence of early-onset sepsis in infants born to women with clinical chorioamnionitis. J Perinat Med 46:926-933
Clark, Erin A S; Weiner, Steven J; Rouse, Dwight J et al. (2018) Genetic Variation, Magnesium Sulfate Exposure, and Adverse Neurodevelopmental Outcomes Following Preterm Birth. Am J Perinatol 35:1012-1022
Askie, Lisa M; Darlow, Brian A; Finer, Neil et al. (2018) Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-analysis Collaboration. JAMA 319:2190-2201
Saade, G R; Thom, E A; Grobman, W A et al. (2018) Cervical funneling or intra-amniotic debris and preterm birth in nulliparous women with midtrimester cervical length less than 30 mm. Ultrasound Obstet Gynecol 52:757-762
Inker, Lesley A; Grams, Morgan E; Levey, Andrew S et al. (2018) Relationship of Estimated GFR and Albuminuria to Concurrent Laboratory Abnormalities: An Individual Participant Data Meta-analysis in a Global Consortium. Am J Kidney Dis :
Juraschek, Stephen P; Miller 3rd, Edgar R; Appel, Lawrence J (2018) Orthostatic Hypotension and Symptoms in the AASK Trial. Am J Hypertens 31:665-671
Younge, Noelle; Goldstein, Ricki F; Bann, Carla M et al. (2017) Survival and Neurodevelopmental Outcomes among Periviable Infants. N Engl J Med 376:617-628
Bustos, Martha L; Caritis, Steve N; Jablonski, Kathleen A et al. (2017) The association among cytochrome P450 3A, progesterone receptor polymorphisms, plasma 17-alpha hydroxyprogesterone caproate concentrations, and spontaneous preterm birth. Am J Obstet Gynecol 217:369.e1-369.e9
Chen, Teresa K; Appel, Lawrence J; Grams, Morgan E et al. (2017) APOL1 Risk Variants and Cardiovascular Disease: Results From the AASK (African American Study of Kidney Disease and Hypertension). Arterioscler Thromb Vasc Biol 37:1765-1769
Srinivasan, Lakshmi; Page, Grier; Kirpalani, Haresh et al. (2017) Genome-wide association study of sepsis in extremely premature infants. Arch Dis Child Fetal Neonatal Ed 102:F439-F445

Showing the most recent 10 out of 753 publications