How Pregnant Women and Their Babies Metabolize Ondansetron Compared to a Group of Non-pregnant Women
How Pregnant Women and Their Babies Metabolize Ondansetron Compared to a Group of Non-pregnant Women
This is called "Aim 1" of the investigators' NIH grant. Ondansetron (Zofran) is a safe and
 effective drug used in pregnant women to prevent nausea but the investigators do not know
 what effect pregnancy may have on the metabolism of Zofran in pregnant women or their babies.
 Therefore the investigators will enroll approximately 40 pregnant women and their babies and
 draw blood samples from the mother, the baby and the cord, to determine how much Zofran is in
 each sample of blood (called the pharmacokinetics or PK of Zofran). The pregnant women will
 receive Zofran, as a standard-of-care drug, for their scheduled Cesarean Section.

 The investigators will also enroll about 20 non-pregnant women undergoing surgery who will
 receive Zofran as standard-of-care during surgery. In both the pregnant & the non-pregnant
 women, the investigators will draw blood samples at the same time points based on number of
 minutes from the time the Zofran is given. The blood data (PK of Zofran) will help the
 investigators move into Aim 2 of the study, which will be done in pregnant, narcotic-addicted
 mothers and their babies who are born addicted to narcotics. Aim 2 will be listed separately
 as it will be an interventional study.
This phase of the study is Aim 1 and it will lead to Aim 2, which specifically will address
 the Prevention of Neonatal Abstinence Syndrome (NAS).

 NAS is a constellation of narcotic drug withdrawal symptoms that develops in 42-94% of the
 infants born to narcotic dependent mothers. This severe syndrome, of which there are no
 preventative treatments, can result in prolonged hospitalization, some of which may be in the
 neonatal intensive care unit (NICU). The investigators have shown that ondansetron can
 eliminate or alleviate the symptoms of narcotic drug withdrawal in experimental studies in
 mice and in humans. Based upon these results, it is quite possible that ondansetron
 administration to pregnant narcotic-using mothers just prior to delivery, followed by a 3-day
 period of ondansetron administration to the neonate, could reduce the incidence or severity
 of NAS symptoms.

 AIM 1 is a pharmacokinetic (PK) study of intravenous (IV) ondansetron in three different
 groups of participants: Study Group #1 = non-pregnant women undergoing surgery; Study Group
 #2 = pregnant women scheduled for cesarean section delivery; Study Group #3 = viable, full
 term, singleton neonates born to study group #2 mothers. Group #1 will be given IV
 ondansetron prior to their surgery and up to 5 PK blood samples will be drawn from an
 indwelling IV line or by IV stick. The PK samples will be 2-5 ml each and will be drawn at
 baseline (prior to ondansetron) and then at 7, 15, and 40 min and 8 hours after the
 ondansetron. Group #2 will be given IV ondansetron prior to their cesarean section and up to
 6 PK blood samples will be drawn from an indwelling IV line or by IV stick. The PK samples
 will be 2-5 ml each and will be drawn at baseline, 7, 15, 40 min and prior to delivery and 8
 hours after the ondansetron is given. The Group #3 neonates will provide a section of the
 umbilical cord from which arterial and venous blood samples will be drawn (this section of
 cord would normally be thrown out and the parents are consenting to allow the Investigators
 to take these two samples). Each time the baby has a "Standard-of-Care" lab test ordered by
 heel stick or needle stick, the investigators will obtain a few drops of blood to place on
 the special research filter paper to determine how much ondansetron is in the baby's blood.
 If the parents will allow any extra heel sticks, the Investigators will try to obtain 1-2
 samples of blood in the first 6 hours of life. If the parents only want their baby's blood
 taken at the standard-of-care lab draws, then the first scheduled lab draw is at 24 hours of
 life for the newborn screening which is a mandated by state law. All blood samples taken for
 this study are being processed by the investigator, not the Stanford Lab. Also, the
 investigators are doing the PK analysis of the dried blood spots on the filter paper and the
 analysis of the frozen plasma samples.

 Aim 2 of this NIH grant will be entered separately into ClinicalTrials.gov. It will be a
 multi-center, randomized, double-blind, placebo-controlled trial to determine whether
 ondansetron treatment will reduce the incidence or severity of NAS in babies born to
 narcotic-using mothers.
Inclusion Criteria:

 For Non-pregnant Females (Group #1)

 1. Age 18-45 yrs inclusive

 2. Generally healthy

 3. Undergoing any scheduled surgical procedure deemed suitable by the Investigator MD

 4. Planned to receive the drug Ondansetron for the surgery

 5. Able and willing to sign the informed consent

 For Pregnant Females (Group #2)

 1. Age 18-45 yrs inclusive

 2. Term pregnancy (37 weeks through 41 wks + 6 days)

 3. Generally healthy (not morbidly obese)

 4. Undergoing a planned C-section or by an unplanned, non-urgent C-section

 5. Planned to receive the drug Ondansetron for the surgery

 6. Single birth

 7. Able and willing to sign the informed consent for herself & the baby

 For the Neonatal Participant (Group #3)

 1. Male or female

 2. Viable birth

 3. Gestational age of 37 weeks through 41 weeks + 6 days

 4. Mother gave written consent for baby to participate

 Exclusion Criteria:

 1. Medical condition that would effect the metabolism of ondansetron

 2. Known allergy to ondansetron

 3. Use of medications in the last 48 hours, by the pregnant or non-pregnant subjects,
 that might induce or inhibit the metabolism of ondansetron (such as CYP3A4 inhibitors
 or inducers)