Two difficult pregnancies inspired pharmacology researcher’s work

When she began studying to be a pharmacist, Mary Hebert imagined that she’d work in a drugstore, perhaps one day work for her dad’s small-town business. Then she caught the research bug and began studying how medications work and interact in liver transplantation patients.

Then she got pregnant. And after two very difficult pregnancies, Hebert, a UW professor of pharmacy and adjunct professor of obstetrics and gynecology, realized that she could apply the same skills she used in studying transplantation to obstetrics as well. “Despite the fact that half the population is female, and most women have at least one child in their life, we knew so little about medications” in pregnancy, she recalls thinking.

Now, Hebert is head of the UW Obstetric-Fetal Pharmacology Research Unit (OPRU), which recently received a $5 million grant from the National Institute of Child Health and Human Development (NICHD) to continue its work on the clinical pharmacology of medications during pregnancy.

The interdisciplinary unit, established in 2004, is one in a network of four centers nationwide conducting research on how pregnant women’s bodies handle and respond to medications. The need for such research is acute, since the average pregnant woman takes two medications (not including prenatal vitamins or drugs administered during delivery), either for chronic health problems such as asthma or high blood pressure, or for pregnancy complications such as gestational diabetes.

Hebert has large, inquisitive brown eyes and short hair in shades of brown sprinkled with gray. She wears black pants and a plain white shirt, so unadorned that the pager and gold key worn at her waist almost read as accessories. In short, she’s not one to call attention to herself.

I just wanted other people to have healthy pregnancies.

Mary Hebert

And in some ways, that goes for her work, too. Despite her intense personal connection to the questions she’s investigating, Hebert is quick to shift the focus elsewhere: “I just wanted other people to have healthy pregnancies,” she says.

Most of what’s known about medications during pregnancy has to do with safety, particularly for the fetus. But while safety is a paramount concern, it isn’t the only one. “Physiologic changes that occur during pregnancy alter the way women’s bodies handle medication,” explains Hebert.

For example, during pregnancy, kidney function increases by up to 60 percent, meaning that drugs excreted by the kidneys are often removed from the body much faster than they are in women who aren’t pregnant. In addition, work by Hebert’s group has shown that some liver enzymes involved in drug metabolism increase in function during pregnancy, so that the drugs they act on are broken down faster than in a nonpregnant woman; other such enzymes decrease in function, so other drugs are broken down more slowly than normal.

In turn, these changes can affect proper medication selection and dosage—but almost nothing was known about how. To begin to answer these questions, Hebert pulled together a team including Thomas Easterling, professor of obstetrics and gynecology; Danny Shen, professor and chair of pharmacy; Kenneth Thummel, professor and chair of pharmaceutics; associate professors of pharmaceutics Qingcheng Mao and Joanne Wang; and Yvonne Lin, assistant professor of pharmaceutics.

The group draws on their different specialties to take studies from basic science through clinical practice. As the OPRU’s principal investigator, Hebert develops the vision that guides the work. She wanted to focus first on gestational diabetes, a condition that affects between 5 percent and 13 percent of pregnancies.

Already, the team has shown that glyburide and metformin, two of the most commonly prescribed oral medications to control blood sugar in women with gestational diabetes, are eliminated much more rapidly in pregnant women. In fact, a pregnant woman needs more than twice the dosage of glyburide as her non-pregnant counterpart in order to achieve the same concentration in the blood. However, the team also discovered that glyburide crosses the placenta—contrary to what was previously thought—raising new safety questions, since increasing the mother’s dose of the drug will also increase her baby’s exposure to it.

Over the next several years, the entire four-center OPRU network will be guided by Hebert’s research vision: the other units have chosen to pursue a plan Hebert’s group proposed to study glyburide and metformin alone and in combination in order to determine the best protocol for treatment of gestational diabetes. Should women get one drug or both? What is the optimum dosage?

Ultimately, Hebert hopes that work in this field will begin to change the prevailing attitude that women simply shouldn’t take any medications during pregnancy. Hebert argues that people are often too quick to say that medications aren’t safe during pregnancy, without evaluating the risks of the underlying illness. If pregnant women have health problems that require medication, “they shouldn’t just suffer through it,” she says.