Pharmacokinetics of amlodipine besylate at delivery and during lactation

Jamie L. Morgan, Benjamin K. Kogutt, Claudia Meek, Elizabeth K. Stehel, Donald D. McIntire, Jeanne S. Sheffield, Scott W. Roberts

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Amlodipine is rarely used in the treatment of pregnant hypertensive women due to limited pharmacokinetic data during pregnancy and the postpartum period. Objective: To evaluate the pharmacokinetics of amlodipine besylate in the peri-partum period including quantities of placental passage, breast milk excretion and infant exposure. Study design: This was a prospective study of pregnant women who were prescribed 5 mg of amlodipine daily for treatment of chronic hypertension and delivered at term. Cord and maternal blood samples were collected at delivery. On postpartum day 2, six paired maternal plasma and breast milk samples were obtained at 4, 6, 8, 12, 15 and 24 h following amlodipine dosing. Infant plasma samples were collected 24–48 h after delivery. All samples were analyzed for amlodipine concentration. A one compartment, first-order model was used to calculate pharmacokinetic estimates for maternal plasma. Results: Of the 16 patients enrolled in the study, 11 had cord blood and maternal serum collected at delivery, of which only 6 produced sufficient breast milk for sampling. Amlodipine was detected in infant cord blood plasma with a mean concentration of 0.49 ± 0.29 ng/mL compared to mean maternal serum level of 1.27 ± 0.84 ng/mL. Amlodipine concentrations in both in breast milk and infant plasma were undetectable at the lower limit of assay detection (<0.1 ng/mL). In the immediate postpartum period, the amlodipine elimination half-life was 13.7 ± 4.9 h, the area under the curve was 53.4 ± 19.8 ng*h/mL and the peak concentration was 2.0 ± 1.0 ng/mL. Conclusions: Amlodipine does cross the placenta in measurable quantities, but is not detected in breast milk or infant plasma at 24–48 h of life indicating that it is likely safe to use during the peripartum period.

Original languageEnglish (US)
Pages (from-to)77-80
Number of pages4
JournalPregnancy Hypertension
Volume11
DOIs
StatePublished - Jan 1 2018

Fingerprint

Amlodipine
Lactation
Pharmacokinetics
Human Milk
Mothers
Fetal Blood
Postpartum Period
Pregnant Women
Peripartum Period
Serum
Placenta
Area Under Curve
Half-Life
Limit of Detection
Prospective Studies
Hypertension
Pregnancy

Keywords

  • Amlodipine
  • Breast milk
  • Chronic hypertension
  • Pharmacokinetics

ASJC Scopus subject areas

  • Internal Medicine
  • Obstetrics and Gynecology

Cite this

Pharmacokinetics of amlodipine besylate at delivery and during lactation. / Morgan, Jamie L.; Kogutt, Benjamin K.; Meek, Claudia; Stehel, Elizabeth K.; McIntire, Donald D.; Sheffield, Jeanne S.; Roberts, Scott W.

In: Pregnancy Hypertension, Vol. 11, 01.01.2018, p. 77-80.

Research output: Contribution to journalArticle

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abstract = "Background: Amlodipine is rarely used in the treatment of pregnant hypertensive women due to limited pharmacokinetic data during pregnancy and the postpartum period. Objective: To evaluate the pharmacokinetics of amlodipine besylate in the peri-partum period including quantities of placental passage, breast milk excretion and infant exposure. Study design: This was a prospective study of pregnant women who were prescribed 5 mg of amlodipine daily for treatment of chronic hypertension and delivered at term. Cord and maternal blood samples were collected at delivery. On postpartum day 2, six paired maternal plasma and breast milk samples were obtained at 4, 6, 8, 12, 15 and 24 h following amlodipine dosing. Infant plasma samples were collected 24–48 h after delivery. All samples were analyzed for amlodipine concentration. A one compartment, first-order model was used to calculate pharmacokinetic estimates for maternal plasma. Results: Of the 16 patients enrolled in the study, 11 had cord blood and maternal serum collected at delivery, of which only 6 produced sufficient breast milk for sampling. Amlodipine was detected in infant cord blood plasma with a mean concentration of 0.49 ± 0.29 ng/mL compared to mean maternal serum level of 1.27 ± 0.84 ng/mL. Amlodipine concentrations in both in breast milk and infant plasma were undetectable at the lower limit of assay detection (<0.1 ng/mL). In the immediate postpartum period, the amlodipine elimination half-life was 13.7 ± 4.9 h, the area under the curve was 53.4 ± 19.8 ng*h/mL and the peak concentration was 2.0 ± 1.0 ng/mL. Conclusions: Amlodipine does cross the placenta in measurable quantities, but is not detected in breast milk or infant plasma at 24–48 h of life indicating that it is likely safe to use during the peripartum period.",
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AU - Sheffield, Jeanne S.

AU - Roberts, Scott W.

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AB - Background: Amlodipine is rarely used in the treatment of pregnant hypertensive women due to limited pharmacokinetic data during pregnancy and the postpartum period. Objective: To evaluate the pharmacokinetics of amlodipine besylate in the peri-partum period including quantities of placental passage, breast milk excretion and infant exposure. Study design: This was a prospective study of pregnant women who were prescribed 5 mg of amlodipine daily for treatment of chronic hypertension and delivered at term. Cord and maternal blood samples were collected at delivery. On postpartum day 2, six paired maternal plasma and breast milk samples were obtained at 4, 6, 8, 12, 15 and 24 h following amlodipine dosing. Infant plasma samples were collected 24–48 h after delivery. All samples were analyzed for amlodipine concentration. A one compartment, first-order model was used to calculate pharmacokinetic estimates for maternal plasma. Results: Of the 16 patients enrolled in the study, 11 had cord blood and maternal serum collected at delivery, of which only 6 produced sufficient breast milk for sampling. Amlodipine was detected in infant cord blood plasma with a mean concentration of 0.49 ± 0.29 ng/mL compared to mean maternal serum level of 1.27 ± 0.84 ng/mL. Amlodipine concentrations in both in breast milk and infant plasma were undetectable at the lower limit of assay detection (<0.1 ng/mL). In the immediate postpartum period, the amlodipine elimination half-life was 13.7 ± 4.9 h, the area under the curve was 53.4 ± 19.8 ng*h/mL and the peak concentration was 2.0 ± 1.0 ng/mL. Conclusions: Amlodipine does cross the placenta in measurable quantities, but is not detected in breast milk or infant plasma at 24–48 h of life indicating that it is likely safe to use during the peripartum period.

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