How Pregnant Women and Their Babies Metabolize Ondansetron Compared to a Group of Non-pregnant Women

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)