Within the world of therapeutics, immense changes have occurred over the last fifty years that have benefited millions. The fundamental purpose of this application for an Obstetric Pharmacology Research Unit is to bring skills and technologies that have been key to the therapeutic revolution to the study of therapeutics in pregnancy. Within a strong academic clinical obstetric environment, we plan to exploit expertise and experience in the discipline of clinical pharmacology, which has been key to the success of the broad therapeutic revolution. We plan to build on the success of our pilot Center, entitled PREGMED, focused on research designed to deliver more individualized care to pregnant women and their children. Our proposal involves the synthesis of strong clinical obstetrics with 5 key cores: 1) a drug analytical laboratory to measure small amounts of drugs in pregnant women and their children;2) a pharmacogenomic core laboratory that will use new high throughput technologies to improve both the targeting of therapies and our understanding of their biochemical basis 3) A computation and bioinformatics core to model pharmacokinetic, pharmacodynamic changes in concert with pharmacogenomic and other biomarker data. 4) An angiogenesis biomarker core aimed at following vascular effects of drugs in these women. 5) a bioethics core that we believe is integral to both our clinical and our basic/preclinical work. To demonstrate the collective value of these cores, we propose linked basic and clinical studies designed to test the vascular effects of the SSRI class of antidepressants in pregnant women. We hypothesize that SSRI metabolism increases during pregnancy resulting in a decrease in patient exposure to the SSRI and subsequent worsening of depressive symptoms and depression scores during pregnancy. To test this hypothesis we propose two aims: i) To investigate the pharmacokinetic parameters and clinical efficacy of SSRI therapy as pregnancy progresses and ii) to examine how genetic polymorphisms of drug metabolizing enzymes and the serotonin pathway impact SSRI disposition and efficacy.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Cooperative Clinical Research--Cooperative Agreements (U10)
Project #
5U10HD063094-05
Application #
8600300
Study Section
Special Emphasis Panel (ZHD1-DSR-Z (02))
Program Officer
Ren, Zhaoxia
Project Start
2010-02-01
Project End
2014-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
5
Fiscal Year
2014
Total Cost
$823,450
Indirect Cost
$264,515
Name
Indiana University-Purdue University at Indianapolis
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
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Pierson, Rebecca C; Gordon, Sashana S; Haas, David M (2014) A retrospective comparison of antibiotic regimens for preterm premature rupture of membranes. Obstet Gynecol 124:515-9
Quinney, Sara K; Patil, Avinash S; Flockhart, David A (2014) Is personalized medicine achievable in obstetrics? Semin Perinatol 38:534-40

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