Pharmacokinetics of Amlodipine Besylate at Delivery and During Lactation

Chronic Hypertension in Pregnancy Clinical Trial

Official title:

Pharmacokinetics of Amlodipine Besylate at Delivery and During Lactation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02353806
• Other study ID #: 042014-059
• Secondary ID: UL1TR001105
• Status: Completed
• Phase: Phase 4
• Start date: January 2015
• Est. completion date: September 2016

Study information

• Verified date: January 2019
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: September 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Hypertension in Pregnancy
• Hypertension
• Hypertension, Pregnancy-Induced
• Pre-Eclampsia

Intervention

Drug:
• Amlodipine besylate
Pregnant and postpartum women will continue taking amlodipine besylate 5 mg for treatment of chronic hypertension as prescribed by their clinician.

Locations

Country	Name	City	State
United States	Parkland Health and Hospital System	Dallas	Texas

Sponsors (2)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center	National Center for Advancing Translational Science (NCATS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Neonatal Birth Weight	The neonatal weight at birth was collected.	Neonatal weight at the time of birth.
Secondary	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
Secondary	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
Secondary	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