The overall objective of this grant proposal is to obtain continued funding for the University of Washington Obstetric-fetal Pharmacology Research Unit (UW OPRU). Pregnant women undergo extensive physiological and biochemical changes not experienced by non-pregnant patients, making them unique with respect to drug therapy selection, dosage, efficacy and safety. Medication use during pregnancy potentially results in fetal exposure and toxicity. On average, women ingest three different drugs during pregnancy;about 66% of these have never been tested in pregnant women. They are administered without the necessary clinical data on the pharmacokinetics, dose, safety, or efficacy during pregnancy. Without such data, the FDA would never approve a drug for the adult non-pregnant population. The impact of insufficient information has translated into either unproven empiric therapy for pregnant women or withholding of critical therapy from women with medically complicated pregnancies. The major goal of the UW OPRU is to identify study and characterize drugs that are of therapeutic value during pregnancy and whose disposition and response are altered by the pregnant state in normal or abnormal pregnancies. The UW OPRU will conduct multidisciplinary, basic, translational and clinical research studies in order to improve care for pregnant women, their fetuses and neonates. The proposed research plan focuses primarily on the gestational age dependent changes in the pharmacokinetics and pharmacodynamics of oral anti-diabetic agents (glyburide and metformin) in the treatment of gestational diabetes mellitus (GDM) and has been developed based upon the following overarching Specific Aims:
Specific Aim 1. Clinical study: To evaluate at 3 stages of treatment (prior to, during initial treatment and after achieving glycemic control) the effects of pregnancy on the PK/PD of glyburide and metformin.
Specific Aim 2. Basic Science and Translational studies: To characterize the time course of and elucidate the biological mechanisms underlying pregnancy-induced changes in drug transporters and drug metabolizing enzymes.
| Ryu, Rachel J; Easterling, Thomas R; Caritis, Steve N et al. (2018) Prednisone Pharmacokinetics During Pregnancy and Lactation. J Clin Pharmacol 58:1223-1232 |
| Caritis, Steve N; Hankins, Gary; Hebert, Mary et al. (2018) Impact of Pregnancy History and 17-Hydroxyprogesterone Caproate on Cervical Cytokines and Matrix Metalloproteinases. Am J Perinatol 35:470-480 |
| Lee, Nora; Hebert, Mary F; Wagner, David J et al. (2018) Organic Cation Transporter 3 Facilitates Fetal Exposure to Metformin during Pregnancy. Mol Pharmacol 94:1125-1131 |
| Kantrowitz-Gordon, Ira; Hays, Karen; Kayode, Olumide et al. (2018) Pharmacokinetics of dacarbazine (DTIC) in pregnancy. Cancer Chemother Pharmacol 81:455-460 |
| Zha, Weibin; Ho, Horace T B; Hu, Tao et al. (2017) Serotonin transporter deficiency drives estrogen-dependent obesity and glucose intolerance. Sci Rep 7:1137 |
| Bergagnini-Kolev, Mackenzie C; Hebert, Mary F; Easterling, Thomas R et al. (2017) Pregnancy Increases the Renal Secretion of N1-methylnicotinamide, an Endogenous Probe for Renal Cation Transporters, in Patients Prescribed Metformin. Drug Metab Dispos 45:325-329 |
| Lemon, Lara S; Zhang, Hongfei; Hebert, Mary F et al. (2016) Ondansetron Exposure Changes in a Pregnant Woman. Pharmacotherapy 36:e139-41 |
| Sharma, Shringi; Caritis, Steve; Hankins, Gary et al. (2016) Population pharmacokinetics of 17?-hydroxyprogesterone caproate in singleton gestation. Br J Clin Pharmacol 82:1084-93 |
| Ryu, Rachel J; Eyal, Sara; Easterling, Thomas R et al. (2016) Pharmacokinetics of metoprolol during pregnancy and lactation. J Clin Pharmacol 56:581-9 |
| Dorfman, E H; Cheng, E Y; Hebert, M F et al. (2016) Prenatal pharmacogenomics: a promising area for research. Pharmacogenomics J 16:303-4 |
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