Individualized Dosing of Nifedipine For Tocolysis in Preterm Labor

The purpose of this study is to identify the relationship between the amount of nifedipine in
a woman's body and its effect on ending preterm (early) labor contractions and delaying
delivery by at least 48 hours. The study will also look at the effects of genes (materials
passed from parent to child that determine the make-up of the body) and other characteristics
(for example mother's age, baby's age, race, and other diseases or drugs) on the ability of
nifedipine to end the contractions. We will use this information to decide what amount of
nifedipine women need to best treat preterm contractions. This study will also examine the
effect of pregnancy on how fast nifedipine is removed from the woman's body.

This study will be conducted on two phases. The first will study women who are starting
nifedipine for treatment of preterm labor. Nifedipine dose will be determined by the
patient's physician. Blood samples will be obtained from the mother to determine the
concentration of nifedipine and its metabolite, oxidized nifedipine, during one dosing
interval. A blood sample will also be obtained for DNA isolation to examine variants in genes
involved in the nifedipine pathway. We will also collect data on uterine contractions and
blood pressure through clinical monitoring. After delivery, maternal and umbilical cord blood
samples will be obtained, along with a piece of placenta. Women who take part in the first
phase will be asked to return 6-10 weeks after delivery. At that time, she will take a single
dose of 10 mg immediate release nifedipine by mouth and blood samples will be collected for
up to 6 hours. Blood pressure will also be monitored prior to collection of each blood sample

Inclusion Criteria:

- Pregnant women 18 years of age or older

- Diagnosed with preterm labor (defined as 1-3 uterine contractions per 10 minute
interval for at least 60 minutes with evidence of change in cervical dilation and/or
effacement)

- Prescribed nifedipine as a tocolytic agent

- Signed informed consent

Exclusion Criteria:

- Multifetal gestation

- Cervical dilation of 5 cm or greater

- Ruptured uterine membranes

- Any medical or obstetrical condition that would contraindicate tocolytic therapy
including placental abruption; placenta previa; nonreassuring fetal status; uterine
growth restriction; severe congenital abnormalities

- Administration of medications known to interact with CYP3A (a human gene) other than
betamethasone or dexamethasone as indicated for stimulating fetal lung maturation,
within the past 24 hours unless approved by study investigators

- Administered a potent mechanism-based CYP3A inhibitor (e.g. erythromycin,
clarithromycin) in past 48 hours

- History of allergy or hypersensitivity to nifedipine

- History of taking grapefruit or grapefruit juice by mouth within the last 24 hours

- Known current hepatic or renal disease