Oxytocin Pharmacokinetics and Pharmacodynamics

Pharmacokinetics and Pharmacodynamics of Oxytocin in Cesarean Delivery

Oxytocin is the first-line drug to promote contraction of the uterus and prevent atony immediately after delivery. Nonetheless, unpredictable uterine atony refractory to oxytocin affects roughly 250,000 parturients annually in the U.S. and rates are increasing. This two-part study will measure the action of oxytocin at cesarean delivery. The first part will measure the pharmacokinetics of a single intravenous (IV) dose of deuterium-labeled oxytocin. The second part will measure the pharmacodynamics of all plasma oxytocin to see how concentrations correspond to the contractile effect on the uterus.

After delivery of the fetus, study subjects will receive a bolus of IV deuterated oxytocin followed by an unlabeled oxytocin infusion. Venous blood samples drawn at multiple time points (within 1 hour after delivery) will be analyzed for plasma concentrations of labeled and unlabeled (endogenous + exogenous infused) oxytocin over time. Plasma concentrations will be compared with 0-10 uterine tone scores measuring uterine contraction strength, to describe the concentration-effect relationship.

The goal of this study is to define both the pharmacokinetics and pharmacodynamics of oxytocin in parturients to help identify the cause(s) of failed first-line oxytocin therapy.

Study Overview

• Status: Recruiting
• Conditions: Blood Loss; Cesarean Section Complications; Post Partum Hemorrhage
• Intervention / Treatment: Drug: deuterated oxytocin (d5OT)

Detailed Description

Parturients aged 18-50 with an intrauterine term pregnancy (37 weeks or greater) undergoing non-emergent cesarean delivery at the University of Chicago (UC) and Stanford University will be recruited.

Methods: All subjects will receive standard pre-, intra- and postoperative care for their cesarean delivery with additional study interventions.

Study subjects will have an additional intravenous (IV) catheter inserted for intra-operative study-related blood draws.

A single, 1 International Unit (IU) bolus of deuterated oxytocin (d5OT) will be given to the subject, followed by an infusion of standard protocol oxytocin immediately after placental delivery. IV samples will be drawn from the study IV at 0, 1, 2.5, 5, 10, 20, 30, 45, 60 minutes following administration of the study drug. The samples will be processed, batched and shipped to the central lab being used in this study. Uterine tone scores will be measured simultaneously with blood draws until accurate palpation is no longer possible. Uterine tone score is a 0 to 10 numeric rating scale with 0 to describe unsatisfactory or no uterine tone and 10 to describe perfect uterine tone.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Naida M Cole, MD; Phone Number: 773-702-6700; Email: nmcole@bsd.uchicago.edu
• Study Contact Backup: Name: Somayeh Mohammadi; Phone Number: 17738343274; Email: mohammadis@bsd.uchicago.edu

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Not yet recruiting
      • Stanford University
      • Contact: Brendan Carvalho, MD; Phone Number: 650-723-6415
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago
      • Contact: Naida M Cole, MD; Phone Number: 773-702-6700; Email: nmcole@bsd.uchicago.edu
      • Contact: Somayeh Mohammadi; Phone Number: 17738343274; Email: mohammadis@bsd.uchicago.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• 18-50 years old
• intrauterine pregnancy
• term (>39 weeks gestation or 37-39 weeks gestation with fetal or maternal medical indication for delivery) pregnancy
• non-emergent (scheduled or unscheduled) cesarean delivery

Exclusion Criteria:

• allergy or contraindication to oxytocin
• inability to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oxytocin PK/PD Arm; Eligible subjects will receive a single, 1 IU bolus of deuterated oxytocin (d5OT) intra-operatively, followed by an infusion of standard therapeutic d0 oxytocin immediately after placental delivery.	Drug: deuterated oxytocin (d5OT); Subjects will receive a 1 IU bolus of deuterated oxytocin (d5OT) intraoperatively during their nonemergent cesarean delivery.; Other Names: Deuterium-labeled oxytocin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline plasma concentrations of deuterated oxytocin	The plasma concentration of deuterium labelled oxytocin at baseline	Intraoperatively (prior to delivery)
Plasma concentrations of deuterated oxytocin at 1 minute	The plasma concentration of deuterium labelled oxytocin at 1 minute post-study drug	Intraoperatively (1 minute following study drug administration)
Plasma concentrations of deuterated oxytocin at 2.5 minutes	The plasma concentration of deuterium labelled oxytocin at 2.5 minutes post-study drug	Intraoperatively (2.5 minutes following study drug administration)
Plasma concentrations of deuterated oxytocin at 5 minutes	The plasma concentration of deuterium labelled oxytocin at 5 minutes post-study drug	Intraoperatively (5 minutes following study drug administration)
Plasma concentrations of deuterated oxytocin at 10 minutes	The plasma concentration of deuterium labelled oxytocin at 10 minutes post-study drug	Intraoperatively (10 minutes following study drug administration)
Plasma concentrations of deuterated oxytocin at 15 minutes	The plasma concentration of deuterium labelled oxytocin at 15 minutes post-study drug	Intraoperatively (15 minutes following study drug administration)
Plasma concentrations of deuterated oxytocin at 20 minutes	The plasma concentration of deuterium labelled oxytocin at 20 minutes post-study drug	Intraoperatively (20 minutes following study drug administration)
Plasma concentrations of deuterated oxytocin at 30 minutes	The plasma concentration of deuterium labelled oxytocin at 30 minutes post-study drug	Intraoperatively (30 minutes following study drug administration)
Plasma concentrations of deuterated oxytocin at 45 minutes	The plasma concentration of deuterium labelled oxytocin at 45 minutes post-study drug	Intraoperatively (45 minutes following study drug administration)
Plasma concentrations of deuterated oxytocin at 60 minutes	The plasma concentration of deuterium labelled oxytocin at 60 minutes post-study drug	Intraoperatively (60 minutes following study drug administration)
0-10 Uterine Tone Score	Uterine tone will be ranked by the obstetrician on a 0-10 scale by palpation of the uterus. A score of 0 will represent 'no tone' and a score of 10 will represent 'perfect tone'. The relationship between plasma concentrations and clinical effect will be determined for pharmacodynamic modeling.	Intraoperatively (at the time of study drug administration)
0-10 Uterine Tone Score	Uterine tone ranked by the obstetrician on a 0-10 scale by palpation of the uterus. A score of 0 will represent 'no tone' and a score of 10 will represent 'perfect tone'. The relationship between plasma concentrations and clinical effect will be determined for pharmacodynamic modeling.	Intraoperatively (1 minute following study drug administration)
0-10 Uterine Tone Score	Uterine tone ranked by the obstetrician on a 0-10 scale by palpation of the uterus. A score of 0 will represent 'no tone' and a score of 10 will represent 'perfect tone'. The relationship between plasma concentrations and clinical effect will be determined for pharmacodynamic modeling.	Intraoperatively (2.5 minutes following study drug administration)
0-10 Uterine Tone Score	Uterine tone ranked by the obstetrician on a 0-10 scale by palpation of the uterus. A score of 0 will represent 'no tone' and a score of 10 will represent 'perfect tone'. The relationship between plasma concentrations and clinical effect will be determined for pharmacodynamic modeling.	Intraoperatively (5 minutes following study drug administration)
0-10 Uterine Tone Score	Uterine tone ranked by the obstetrician on a 0-10 scale by palpation of the uterus. A score of 0 will represent 'no tone' and a score of 10 will represent 'perfect tone'. The relationship between plasma concentrations and clinical effect will be determined for pharmacodynamic modeling.	Intraoperatively (10 minutes following study drug administration)
0-10 Uterine Tone Score	Uterine tone ranked by the obstetrician on a 0-10 scale by palpation of the uterus. A score of 0 will represent 'no tone' and a score of 10 will represent 'perfect tone'. The relationship between plasma concentrations and clinical effect will be determined for pharmacodynamic modeling.	Intraoperatively (15 minutes following study drug administration)
0-10 Uterine Tone Score	Uterine tone ranked by the obstetrician on a 0-10 scale by palpation of the uterus. A score of 0 will represent 'no tone' and a score of 10 will represent 'perfect tone'. The relationship between plasma concentrations and clinical effect will be determined for pharmacodynamic modeling.	Intraoperatively (20 minutes following study drug administration)
0-10 Uterine Tone Score	Uterine tone ranked by the obstetrician on a 0-10 scale by palpation of the uterus. A score of 0 will represent 'no tone' and a score of 10 will represent 'perfect tone'. The relationship between plasma concentrations and clinical effect will be determined for pharmacodynamic modeling.	Intraoperatively (30 minutes following study drug administration)
0-10 Uterine Tone Score	Uterine tone ranked by the obstetrician on a 0-10 scale by palpation of the uterus. A score of 0 will represent 'no tone' and a score of 10 will represent 'perfect tone'. The relationship between plasma concentrations and clinical effect will be determined for pharmacodynamic modeling.	Intraoperatively (45 minutes following study drug administration)
0-10 Uterine Tone Score	Uterine tone ranked by the obstetrician on a 0-10 scale by palpation of the uterus. A score of 0 will represent 'no tone' and a score of 10 will represent 'perfect tone'. The relationship between plasma concentrations and clinical effect will be determined for pharmacodynamic modeling.	Intraoperatively (60 minutes following study drug administration)

Collaborators and Investigators

• Sponsor: University of Chicago
• Collaborators: Stanford University
• Investigators: Principal Investigator: Naida M Cole, MD, University of Chicago

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: July 19, 2022
• First Submitted That Met QC Criteria: August 2, 2022
• First Posted (Actual): August 4, 2022

Study Record Updates

• Last Update Posted (Estimated): October 3, 2025
• Last Update Submitted That Met QC Criteria: October 1, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Oxytocin; Postpartum; Parturients; pharmacokinetics and Pharmacodynamics; Uterine Tone; Elective C-Section
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor Complications; Pregnancy Complications; Puerperal Disorders; Uterine Hemorrhage; Pathological Conditions, Signs and Symptoms; Postpartum Hemorrhage; Hemorrhage; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: IRB24-0480

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No