The discovery of penicillin led to the development of natural, semi-synthetic, and synthetic antimicrobial medications. Quickly thereafter, resistant strains of microorganisms began appearing around the globe. Methicillin-resistant S. aureus, especially community-acquired MRSA, is increasingly a problem in pregnant women and in the postpartum period. The rate of MRSA infections in pregnant women, between 2000 and 2004, increased 10-fold. Postparturritional infections due to the MRSA are often serious and potentially life- threatening. Vancomycin has been the antibiotic of choice for treatment of infections caused by MRSA;however, the development of vancomycin-resistant strains of Staphylococcus aureus (VRSA) compromised its use and led to the development of its derivative telavancin. However, neither medication is approved for treatment of these infections in the pregnant patient. The hypoithesis for the proposed work is that changes in maternal physiology during pregnancy and the development of the feto-placental compartment will affect drug disposition and, consequently, pharmacokinetics (PK) and pharmacodynamics (PD) of vancomycin and telavancin. Therefore, the goal of the clinical pharmacology and translational projects proposed is to provide fundamental and necessary information that is elemental in making these 2 medications available for treatment of MRSA and VRSA infections during pregnancy. To achieve this goal, the following specific aims will be investigated: For the clinical trial-(1) The PK of vancomycin and telavancin, (2) Perinatal and maternal outcome, and (3) Neonatal outcome. For the translational project-(1) Determine the ex vivo placental transfer of the 2 antibiotics, (2) Identify the enzymes responsible for their biotransformation and the metabolites formed, (3) Determine the role and activity of placental uptake and efflux transporters and their effect on the extent of fetal exposure to the 2 antibiotics, and (4) Determine the effect of polymorphisms in the genes expressing the responsible metabolizing enzymes and transporters on their activity. The data obtained will provide the most basic information required for determination of the dose of each medication administered during pregnancy;its effect on perinatal, maternal, and neonatal outcomes;the extent to which the placenta regulates its transfer to the fetal circulation;and whether it is affected by genetic variables that could be liked to ethnicity of either the mother, fetus, or both.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Cooperative Clinical Research--Cooperative Agreements (U10)
Project #
Application #
Study Section
Special Emphasis Panel (ZHD1-DSR-Z (02))
Program Officer
Ren, Zhaoxia
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Texas Medical Br Galveston
Obstetrics & Gynecology
Schools of Medicine
United States
Zip Code
Ryu, Rachel J; Easterling, Thomas R; Caritis, Steve N et al. (2018) Prednisone Pharmacokinetics During Pregnancy and Lactation. J Clin Pharmacol 58:1223-1232
Speidel, Jordan T; Xu, Meixiang; Abdel-Rahman, Sherif Z (2018) Bisphenol A (BPA) and bisphenol S (BPS) alter the promoter activity of the ABCB1 gene encoding P-glycoprotein in the human placenta in a haplotype-dependent manner. Toxicol Appl Pharmacol 359:47-54
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
Gopalakrishnan, Kathirvel; More, Amar S; Hankins, Gary D et al. (2017) Postnatal Cardiovascular Consequences in the Offspring of Pregnant Rats Exposed to Smoking and Smoking Cessation Pharmacotherapies. Reprod Sci 24:919-933
Fokina, Valentina M; Xu, Meixiang; Rytting, Erik et al. (2016) Pharmacokinetics of Bupropion and Its Pharmacologically Active Metabolites in Pregnancy. Drug Metab Dispos 44:1832-1838
Zhang, Xing; Vernikovskaya, Daria I; Wang, Xiaoming et al. (2016) Quantitative determination of pravastatin and its metabolite 3?-hydroxy pravastatin in plasma and urine of pregnant patients by LC-MS/MS. Biomed Chromatogr 30:548-54
Lemon, Lara S; Zhang, Hongfei; Hebert, Mary F et al. (2016) Ondansetron Exposure Changes in a Pregnant Woman. Pharmacotherapy 36:e139-41
Ryu, Rachel J; Eyal, Sara; Easterling, Thomas R et al. (2016) Pharmacokinetics of metoprolol during pregnancy and lactation. J Clin Pharmacol 56:581-9
Fokina, Valentina M; West, Holly; Oncken, Cheryl et al. (2016) Bupropion therapy during pregnancy: the drug and its major metabolites in umbilical cord plasma and amniotic fluid. Am J Obstet Gynecol 215:497.e1-7
Costantine, Maged M; Cleary, Kirsten; Hebert, Mary F et al. (2016) Safety and pharmacokinetics of pravastatin used for the prevention of preeclampsia in high-risk pregnant women: a pilot randomized controlled trial. Am J Obstet Gynecol 214:720.e1-720.e17

Showing the most recent 10 out of 44 publications