Jamie L Morgan1, Benjamin K Kogutt2, Claudia Meek3, Elizabeth K Stehel4, Donald D McIntire2, Jeanne S Sheffield5, Scott W Roberts2. 1. Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, United States. Electronic address: jamie.morgan@utsouthwestern.edu. 2. Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, United States. 3. Clinical Pharmacology and Experimental Therapeutics Center, Texas Tech School of Pharmacy, Dallas, TX, United States. 4. Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, United States. 5. Department of Obstetrics and Gynecolgy, Johns Hopkins School of Medicine, Baltimore, MD, United States.
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.
BACKGROUND:Amlodipine is rarely used in the treatment of pregnant hypertensivewomen 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.
Authors: Ian R Mulrenin; Julian E Garcia; Muluneh M Fashe; Matthew Shane Loop; Melissa A Daubert; Rachel Peragallo Urrutia; Craig R Lee Journal: Expert Opin Drug Metab Toxicol Date: 2021-11 Impact factor: 4.481