Study could prove beneficial to improving drug therapy during pregnancy

May 1, 2014

More than 50% of pregnant women take at least one medication, and the average number of prescriptions per patient during pregnancy ranges from three to five. Pregnancy is known to alter the rate and extent of drug elimination posing a challenge to prescribers. At the same time, current obstetric guidelines promote the use of appropriate (i.e., "lowest effective") doses of drugs to prevent adverse outcomes in fetuses. However, determining "appropriate" dosing has been difficult as very little is understood about what causes these changes in drug disposition during pregnancy. A better understanding of altered drug disposition during pregnancy and its underlying mechanisms is critical to determine optimal dosage regimens in pregnant women.

Hyunyoung Jeong, an associate professor at the University of Illinois at Chicago, uses human liver cells to identify factors causing changes in the rate of hepatic elimination. Previously, her work highlighted important roles of multiple such as estrogens and progesterone in such changes. What she discovered is that most hormones alter the expression of many enzymes involved in hepatic drug metabolism—but not an enzyme called CYP2D6. CYP2D6 is an important drug-metabolizing enzyme that is responsible for the elimination of 20% of marketed drugs. Jeong's latest study is the first to identify factors that govern CYP2D6 induction during pregnancy.

The study first established "CYP2D6-humanized mice" as a model to study CYP2D6 induction during pregnancy. These mice carry the human CYP2D6 gene so that the well-known interspecies difference in the genes of drug-metabolizing enzymes could be overcome. In the mice, a transcription factor called SHP was shown to exhibit decreased expression in the liver during pregnancy. Follow-up mechanistic studies revealed that SHP is a negative regulator of CYP2D6 expression, suggesting that decreased SHP expression may explain CYP2D6 induction during pregnancy. To identify upstream regulators of SHP that trigger the phenomenon, different factors that are known to alter SHP expression were screened. Hepatic levels of retinoic acid, a bioactive product of dietary vitamin A and an inducer of SHP expression, was decreased in mouse livers during pregnancy.

The identification of factors underlying CYP2D6 induction during pregnancy would be a major advance in improving drug therapy during pregnancy.

Explore further: Ability to metabolize tamoxifen affects breast cancer outcomes, study confirms

More information: Dr. Jeong presented the findings during the Experimental Biology 2014 meeting on Sunday, April 30 from at the Effects of Drugs, Genetics and Pregnancy on Drug Metabolism poster session in the Sails Pavilion (Poster #W417) of the San Diego Convention Center.

Related Stories

Ability to metabolize tamoxifen affects breast cancer outcomes, study confirms

December 27, 2012
For nearly a decade, breast cancer researchers studying the hormone therapy tamoxifen have been divided as to whether genetic differences in a liver enzyme affect the drug's effectiveness and the likelihood breast cancer ...

Cold winters freezing out breast cancer treatment

April 18, 2013
For women diagnosed with a form of breast cancer known as estrogen receptor positive (ER+) breast cancer, tamoxifen is an essential drug used in the treatment and prevention of recurring breast cancer. Currently, tamoxifen ...

Bipolar drugs lose effect during pregnancy, so women need higher doses to stay well

November 1, 2013
New Northwestern Medicine research offers one of the first in-depth studies of how physiological changes during pregnancy reduce the effects of a commonly used drug to treat bipolar disorder, making women more vulnerable ...

Mother's immunosuppressive medications not likely to put fetus at risk

November 8, 2013
Women with chronic autoimmune diseases who take immunosuppressive medications during their first trimester of pregnancy are not putting their babies at significantly increased risk of adverse outcomes, according to a Vanderbilt ...

Malaria drug combo could help prevent pregnancy complications in lupus patients

January 22, 2014
An anti-malaria drug combination might be useful in helping to prevent pregnancy complications in women with lupus and the related disorder antiphospholipid syndrome, Yale School of Medicine researchers have found in a new ...

Progesterone test can predict viability of pregnancy

September 27, 2012
Measuring progesterone levels in women with pain or bleeding during early pregnancy is a useful way to help discriminate between a viable and a non-viable pregnancy, finds a study published in the British Medical Journal ...

Recommended for you

Women exposed to smoke while in womb more likely to miscarry

July 13, 2017
Women exposed to cigarette smoke while in their mothers' wombs are more likely to experience miscarriage as adults, according to new research from the University of Aberdeen.

Lack of a hormone in pregnant mice linked to preeclampsia

June 30, 2017
(Medical Xpress)—A team of researchers from Singapore, the Netherlands and Turkey has isolated a hormone in pregnant mice that appears to be associated with preeclampsia—a pregnancy-related condition characterized by ...

Aspirin reduces risk of pre-eclampsia in pregnant women

June 28, 2017
Taking a low-dose aspirin before bed can reduce the risk of pre-eclampsia, which can cause premature birth and, in extreme cases, maternal and foetal death.

The biology of uterine fluid: How it informs the fetus of mom's world

June 22, 2017
A developing fetus bathes in a mixture of cellular secretions and proteins unique to its mother's uterus. Before fertilization, the pH of uterine fluid helps create a conducive environment for sperm migration, and afterward, ...

New clues in puzzle over pre-eclampsia and cholesterol regulation

June 21, 2017
Scientists studying a mystery link between the dangerous pregnancy complication pre-eclampsia and an increased risk of heart disease in later life for both mother and child have uncovered important new clues.

Are maternal hormones different when carrying a boy or a girl?

June 15, 2017
With advances in prenatal testing it's now possible to find out whether a pregnancy will result in a male or female baby as early as eight weeks' gestation.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.