“The safety and effectiveness of this drug has not been established in pregnancy.”
If up to UTMB researchers, those cautionary words on medication labels may soon be a thing of the past.
The study of drugs given to pregnant women is one of the most neglected areas in the field of clinical pharmacology and drug research. As such, only a handful of medications have been approved by the Food and Drug Administration for use in pregnancy.
“Pregnancy poses a unique situation,” said Dr. Gary Hankins, chairman of the Department of Obstetrics and Gynecology, explaining the dearth of research. “Pharmaceutical companies, because of fears of fetal harm and financial loss resulting from liability claims, have been reluctant to study drugs in pregnancy. It’s a challenge.”
But a challenge that UTMB is uniquely qualified to handle.
UTMB has long been a leader in maternal-fetal medicine and research — 10 years as part of a network of sites studying medications in pregnancy. The National Institutes of Health recognized UTMB’s emergence as a national resource and recently awarded it $5.3 million to establish an Obstetric-Fetal Pharmacology Research Center, of which there are only three in the nation.
While remarkable progress has been made in research over the past few years, significant knowledge gaps remain. Using a multidisciplinary approach, UTMB’s research center — called the Center for Development of Medications and Biologics for Treatment of the Pregnant Patient and Fetus — will help with the translation of knowledge from the basic sciences into the development of new treatments, and findings from clinical trials into practice, with the ultimate goal of improving the safety and effectiveness of medications for pregnant women.
A 2011 study reported that most women (90 percent) take at least one medication during pregnancy. Consider that the size of the kidneys, plasma volume, and cardiac output all increase by 50 percent during pregnancy, and common sense tells you that the dosage for pregnant women would not be the same as for nonpregnant women.
Mahmoud S. Ahmed, Ph.D., director of the Maternal-Fetal Pharmacology and Bio-development Laboratories, explains, “Pregnancy causes extensive physiological and biochemical changes in the mother that are currently not accounted for in medicine. A number of variables can modify the intensity and duration of a drug’s effect, including absorption, excretion, blood flow and interaction with other compounds.”
He said obtaining clinical data is imperative to gaining FDA approval for medications in pregnancy. The center will study a wide range of acute and chronic conditions, as well as pregnancy complications.
The center’s three initial research projects will include a clinical, a translational and a pilot project. The pilot will evaluate nanomedicine tools (matter at the molecular level) for safety and efficacy in treating cancer during pregnancy. The translational and clinical projects will work together to establish optimal dosing of the prescription drug pravastatin to prevent preeclampsia — a condition that affects blood pressure and results in 500,000 infant deaths worldwide each year.
The preliminary results of the pravastatin study are astounding, according to Hankins. “If they hold, this will be the most significant contribution I’ve made in my life,” he said. “We are truly doing things that have never been done before in obstetric-fetal medicine. In fact, the medicine we practice today, other places won’t practice for a decade — we are that far ahead. We’re defining the medicine of tomorrow. And that’s the truth.”
Left to right (back): Wayne Snodgrass, Maged Constantine, Erik Rytting, Gary D.V. Hankins. Left to right (front): Sherif Z. Abdel-Rahman, Holly West, Mahmoud S. Ahmed, Tatiana N. Nanovskaya. Not pictured: Shannon Clark, Mahbubur, Rahman, Xiao-Ming Wang.
History
The first interdisciplinary team of investigators was achieved by building on the existing collaboration between Hankins, a clinical scientist, and Ahmed, a translational scientist, which started in 2002 and resulted in numerous NIH grants that were competitively renewed. The pair focused on (1) recruiting new faculty members and selecting and training the second generation of clinical and research scientists and (2) providing the environment and resources required for building a multidisciplinary team of investigators capable of launching clinical and translational projects. In 2008, Ahmed submitted a five-year strategic plan for building a new division in the department, out of which the Maternal-fetal Pharmacology and Biodevelopment Laboratories was formed. The mission: to form multidisciplinary teams of clinical and translational investigators interested in women’s health, with one team focused on maternal-fetal pharmacology.
Center’s team:
The center’s director is Gary Hankins, M.D., and associate director is Mahmoud S. Ahmed, Ph.D.
UTMB clinical and research scientists include Sherif Abdel-Rahman, Ph.D.; Shannon Clark, M.D.; Maged Costantine, M.D.; Tatiana Nanovskaya, Ph.D.; Mahbubur Rahman, MBBS, Ph.D., MPH; Erik Rytting, Ph.D.; Wayne Snodgrass, M.D., Ph.D.; Xiao-Ming Wang, Ph.D.; and Holly West, DHEd. Collaborators include Susan Abdel-Rahman, Pharm.D., from Children’s Mercy Hospital in Kansas City, Missouri, and Kimberly Dukes, Ph.D., CEO of DM-STAT.