Pharmacokinetics of Amlodipine Besylate at Delivery and During Lactation

Study Overview
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Brief Summary
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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
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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.

Official Title
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Pharmacokinetics of Amlodipine Besylate at Delivery and During Lactation

Conditions
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Chronic Hypertension in Pregnancy

Intervention / Treatment
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* Drug: Amlodipine besylate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pregnant women taking amlodipine<br>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<br>* Pregnant and postpartum women will continue taking amlodipine besylate 5 mg for treatment of chronic hypertension as prescribed by their clinician.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amlodipine besylate, Breast milk, Pharmacokinetics, Chronic hypertension, Pregnancy