How Pregnant Women and Their Babies Metabolize Ondansetron Compared to a Group of Non-pregnant Women
Condition: Postoperative Nausea
MeSH terms: Postoperative Nausea and Vomiting
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Ondansetron
Intervention type(s): Drug
Intervention description(s): Pregnant & non-pregnant women will receive either 4mg or 8mg of Ondansetron (IV) once prior to surgical procedure (open-label). Women are in the study for 8 hours. Babies of pregnant women are not given Ondansetron but are in the study for 24-48 hours.
Other intervention name(s): Zofran
Intervention MeSH terms: Ondansetron
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Keywords: Pharmacokinetics of ondansetron in women; Pharmacokinetics of ondansetron in neonates; Term pregnancy; Cesarean section