Pharmacokinetics of Amlodipine Besylate at Delivery and During Lactation

This is a phase IV prospective trial to collect and analyze information about the maternal pharmacokinetics of amlodipine besylate at the time of delivery and during postpartum lactation. The study will also evaluate amlodipine concentrations in the infants of breastfeeding mothers who are taking amlodipine besylate for treatment chronic hypertension.

Study Overview

• Status: Completed
• Conditions: Chronic Hypertension in Pregnancy
• Intervention / Treatment: Drug: Amlodipine besylate

Detailed Description

We plan to evaluate the pharmacokinetics of amlodipine besylate at the time of delivery, to determine if transplacental passage of the drug occurs. We will also examine the drug kinetics in postpartum lactation to establish whether amlodipine is excreted into breast milk. The outcomes of interest are plasma concentration of amlodipine at delivery and the drug concentrations in blood and breast milk over a twenty-hour steady-state period following milk-supply establishment. Fifteen patients already taking 5 mg of amlodipine during pregnancy for the treatment of chronic hypertension will be recruited from the antepartum Obstetric Complications Clinic at Parkland Hospital. Only women who are breastfeeding will be eligible for the study. Patients who elect to participate in the study will continue their amlodipine 5 mg dosing through delivery and into the postpartum period. Maternal blood will be drawn within one hour of delivery and fetal cord blood collected at the time of delivery. Patients will then have blood drawn over a 24 hour period beginning on postpartum day 2 after delivery following administration of their once-daily amlodipine dose. At each blood draw, the patient will also use a breast pump to express breast milk for paired analysis. Both blood and breast milk amlodipine levels will be calculated for all samples. The levels will be used to determine the pharmacokinetics of amlodipine in the peri- and postpartum patient, including concentrations in plasma and breast milk.

In addition to collecting maternal data, a range of clinical information will be collected on each study patient's infant including weight, Apgar scores, hemodynamic parameters, physical examination and hospital course. This information will be used to screen for any potential complications associated with infant exposure to amlodipine. An infant blood sample will also be obtained in conjunction with the routine neonatal blood collection that occurs at 1-2 days of postnatal life and this will be analyzed to determine serum amlodipine concentration in breastfeeding infants.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75235
      • Parkland Health and Hospital System

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 18 years or older;
• Pregnant female
• Already taking amlodipine 5 mg for treatment of chronic hypertension in pregnancy;
• Hospitalized following routine term vaginal delivery or uncomplicated cesarean delivery
• Breastfeeding or breast and bottle-feeding their infant

Exclusion Criteria:

• Known kidney disease
• Delivery complicated by chorioamnionitis, endometritis or postpartum hemorrhage
• Administration of greater than 5 mg of amlodipine in 24 hour period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: Pregnant women taking amlodipine; Women already taking amlodipine besylate 5 mg for treatment of chronic hypertension in pregnancy who plan to breastfeed postpartum will be assigned to the single experimental arm.	Drug: Amlodipine besylate; Pregnant and postpartum women will continue taking amlodipine besylate 5 mg for treatment of chronic hypertension as prescribed by their clinician.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve for Amlodipine in the Maternal Serum	The time to peak amlodipine concentration in the maternal serum in the peripartum period was be measured.	Maternal blood samples will be obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing
Time to Maximal Concentration in the Maternal Serum.	The time to reach maximal amlodipine concentration in the maternal serum in the peripartum period was measured.	Maternal blood samples were obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing
Maximal Amlodipine Maternal Serum Concentration	The maximum concentration of amlodipine detected in the maternal serum in the peripartum period was measured.	Maternal blood samples were obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing
Half-life of Amlodipine in Maternal Plasma	The half-life of amlodipine in the maternal plasma in the peripartum period was measured.	Maternal blood samples were obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing
Clearance Rate of Plasma Amlodipine	The clearance rate of amlodipine from the maternal plasma was measured.	Maternal blood samples were obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing
Drug Levels/Concentration in Cord Blood (Amlodipine Levels/Concentrations)	Maternal and cord blood amlodipine levels/concentrations will be determined.	Pair maternal blood sample and cord blood sample will draw within 1 hour of delivery
Amlodipine Concentration in Breastmilk	The concentration of amlodipine besylate was measured in breastmilk samples.	Breast milk samples were obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing
Drug Level/Concentration in Infant Blood (Amlodipine Level/Concentration)	Infant amlodipine level/concentration will be determined.	Infant blood sample drawn at approximately 36 hours of life

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neonatal Birth Weight	The neonatal weight at birth was collected.	Neonatal weight at the time of birth.
Infant Gestational Age at Delivery.	The mean gestational age of infants born to mothers taking Amlodipine besylate 5 mg daily was collected.	Gestational age at the time of birth
Infant Length of Stay.	The length of stay of infants born to women taking amlodipine besylate will be collected.	Time from birth to hospital discharge
Major Infant Complications	Any major complications experienced by infants born to women taking amlodipine besylate including NICU admission, intraventricular hemorrhage, neonatal seizures, need for respiratory support and apnea were collected.	During neonatal hospitalization

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: National Center for Advancing Translational Sciences (NCATS)
• Investigators: Principal Investigator: Jamie L Morgan, MD, University of Texas Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: January 26, 2015
• First Submitted That Met QC Criteria: February 2, 2015
• First Posted (Estimate): February 3, 2015

Study Record Updates

• Last Update Posted (Actual): February 6, 2019
• Last Update Submitted That Met QC Criteria: January 15, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Pregnancy; Pharmacokinetics; Breast milk; Amlodipine besylate; Chronic hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Pregnancy Complications; Hypertension; Hypertension, Pregnancy-Induced; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Amlodipine
• Other Study ID Numbers: 042014-059; UL1TR001105 (U.S. NIH Grant/Contract)