Clinical trial NCT02353806: Pharmacokinetics of Amlodipine Besylate at Delivery and During Lactation
Official title: Pharmacokinetics of Amlodipine Besylate at Delivery and During Lactation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Hypertension in Pregnancy
Keywords: Amlodipine besylate
Breast milk
Pharmacokinetics
Chronic hypertension
Pregnancy
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: National Center for Advancing Translational Sciences (NCATS)
First posted: 2015-02-03
Enrollment: 16
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Curve for Amlodipine in the Maternal Serum
timeFrame: Maternal blood samples will be obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing
measure: Time to Maximal Concentration in the Maternal Serum.
timeFrame: Maternal blood samples were obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing
measure: Maximal Amlodipine Maternal Serum Concentration
timeFrame: Maternal blood samples were obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing
measure: Half-life of Amlodipine in Maternal Plasma
timeFrame: Maternal blood samples were obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing
measure: Clearance Rate of Plasma Amlodipine
timeFrame: Maternal blood samples were obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing
measure: Drug Levels/Concentration in Cord Blood (Amlodipine Levels/Concentrations)
timeFrame: Pair maternal blood sample and cord blood sample will draw within 1 hour of delivery
measure: Amlodipine Concentration in Breastmilk
timeFrame: Breast milk samples were obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing
measure: Drug Level/Concentration in Infant Blood (Amlodipine Level/Concentration)
timeFrame: Infant blood sample drawn at approximately 36 hours of life
Secondary outcomes:
measure: Neonatal Birth Weight
timeFrame: Neonatal weight at the time of birth.
measure: Infant Gestational Age at Delivery.
timeFrame: Gestational age at the time of birth
measure: Infant Length of Stay.
timeFrame: Time from birth to hospital discharge
measure: Major Infant Complications
timeFrame: During neonatal hospitalization
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Parkland Health and Hospital System
state: Texas
Study officials:
affiliation: University of Texas Southwestern Medical Center
name: Jamie L Morgan, MD
role: PRINCIPAL_INVESTIGATOR
References: