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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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PK and PD Modeling of Ampicillin and Gentamicin in Peripartum Patients

Conditions
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Drug Metabolism During Pregnancy

Intervention / Treatment
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* Drug: Ampicillin
* Drug: Ampicillin and Gentamicin
* Drug: Gentamicin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pregnant/Ampicillin<br>pregnant participants who will receive Ampicillin for conditions such as Group B Streptococcus | Drug: Ampicillin<br>* 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<br>|
| Non-pregnant/Ampicillin<br>non-pregnant participants who will receive Ampicillin for a qualifying hospital admission | Drug: Ampicillin<br>* 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<br>|
| Pregnant and Non-pregnant/Ampicillin and Gentamicin<br>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<br>* 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<br>|
| Non-Pregnant/Gentamicin<br>non-pregnant participants who will receive Gentamicin for a qualifying hospital admission | Drug: Gentamicin<br>* Prescribed to non-pregnant participants<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics (PK), Pharmacodynamics (PD)