Pharmacokinetic (PK) and Pharmacodynamic (PD) Modeling of Ampicillin and Gentamicin in Peripartum Patients

PK and PD Modeling of Ampicillin and Gentamicin in Peripartum Patients

This study proposes to compare the metabolism of Ampicillin and Gentamicin by pregnant women to that of non-pregnant women; the placental transfer over time; and the subsequent metabolism of the transferred drug(s) in the neonate.

Study Overview

• Status: Completed
• Conditions: Drug Metabolism During Pregnancy
• Intervention / Treatment: Drug: Ampicillin; Drug: Ampicillin and Gentamicin; Drug: Gentamicin

Detailed Description

Pregnant women who present to Labor and Delivery will be identified as potential participants based on Inclusion/Exclusion criteria and their need to receive Ampicillin and/or Gentamicin therapy. The additional group of 20 non-pregnant women will also be identified based on Inclusion/Exclusion criteria and their need to receive Ampicillin and/or Gentamicin therapy.

Once identified, interested candidates will be fully informed of the study procedures, have all questions answered, and informed consent obtained.

Pregnant participants will receive Ampicillin 2g IV loading dose followed by 1g IV every 4 hrs until delivery; or Ampicillin 2g IV every 6hrs along with Gentamicin 5mg/kg IV every 24 hrs. Dose times will be recorded.

Non-pregnant participants will receive similar doses of either Ampicillin and/or Gentamicin, if not the same dose(s).

Fingerstick blood collection will be drawn from both populations at the following timepoints:

• before the administration of Ampicillin, and/or
• before the administration of Gentamicin
• after the full initial dose of the antibiotic has infused, at 5 min, 15 min, 30 min, 2-3hr, 4-6hr, immediately prior to the next dose of drug, and at DELIVERY (a 5 minute window for each timepoint will be permitted) If delivery occurs prior to the 3 or 6 hr timepoints, fingerstick blood collection should continue

Samples will be obtained on filter paper via the Dry Blood Spot (DBS) method, which is clinically appropriate for the purposes of this study.

Umbilical venous and arterial blood will also be drawn for sampling from the placenta after delivery, and cutting of the umbilical cord.

• Study Type: Observational
• Enrollment (Actual): 45

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Lucille Packard Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Women receiving ampicillin or gentamicin

Description

Inclusion Criteria:

• Generally healthy, pregnant woman (28-42 weeks)
• Generally healthy, non-pregnant female
• Scheduled to receive Ampicillin and/or Gentamicin IV
• Ages 18-55 years old
• Relatively normal Comprehensive Metabolic Panel (if available), as evidenced by recent blood work
• Able and willing to sign consent

Exclusion Criteria:

• Women with known renal or hepatic impairment; preeclampsia; Diabetes, including Gestational; any medical condition that, in the opinion of the Investigator or research team member, could potentially interfere with the study objectives
• Women who are participating in another study
• Pregnant with multiples
• BMI > 40

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pregnant/Ampicillin; pregnant participants who will receive Ampicillin for conditions such as Group B Streptococcus	Drug: Ampicillin; Pregnant participants will receive Ampicillin 2g IV loading dose followed by 1g IV every 4 hrs until delivery for Group B Strep prophylaxis; non-pregnant participants will receive Ampicillin for qualifying diagnosis
Non-pregnant/Ampicillin; non-pregnant participants who will receive Ampicillin for a qualifying hospital admission	Drug: Ampicillin; Pregnant participants will receive Ampicillin 2g IV loading dose followed by 1g IV every 4 hrs until delivery for Group B Strep prophylaxis; non-pregnant participants will receive Ampicillin for qualifying diagnosis
Pregnant and Non-pregnant/Ampicillin and Gentamicin; pregnant participants who will receive Ampicillin and Gentamicin for conditions such as chorioamnionitis; non-pregnant participants who will receive Ampicillin and Gentamicin for a qualifying hospital admission	Drug: Ampicillin and Gentamicin; Pregnant participants will receive Ampicillin 2g IV every 6hrs along with Gentamicin 5mg/kg IV every 24 hrs for chorioamnionitis; non-pregnant participants will receive for qualifying diagnosis
Non-Pregnant/Gentamicin; non-pregnant participants who will receive Gentamicin for a qualifying hospital admission	Drug: Gentamicin; Prescribed to non-pregnant participants

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Profiling to Measure Maternal Metabolism of Ampicillin and/or Gentamicin in Pregnancy	blood samples will be taken at the above timepoints; data analysis of all specimens will begin approx. 12-15 months from start of study	predose; after the full initial dose of the antibiotic has infused, at 5min, 15min, 30min, 2-3hr, 4-6hr, immediately prior to the next dose of drug, and at DELIVERY

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Profile of Neonatal Metabolism of Ampicillin and Gentamicin That Crosses the Placental Barrier	blood samples to be drawn at the above timepoint; data analysis of all specimens will begin approx. 12-15 months from start of study	At delivery/upon cutting of umbilical cord
PD Modeling of Peripartum Patients Receiving Ampicillin and/or Gentamicin	subject will be observed for adverse events related to drug administration	predose; while dosing; post dose

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: David Drover, MD
• Investigators: Study Director: Brendan Carvalho, MBBCh, Stanford University; Study Director: David Drover, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2015
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: April 14, 2015
• First Submitted That Met QC Criteria: April 22, 2015
• First Posted (Estimate): April 28, 2015

Study Record Updates

• Last Update Posted (Actual): May 10, 2017
• Last Update Submitted That Met QC Criteria: May 8, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Pharmacokinetics (PK); Pharmacodynamics (PD)
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Ampicillin; Gentamicins
• Other Study ID Numbers: 29664