title: Pharmacokinetics of metoprolol during pregnancy and lactation.
abstract: The objective of this study was to evaluate the steady-state pharmacokinetics of metoprolol during pregnancy and lactation. Serial plasma, urine, and breast milk concentrations of metoprolol and its metabolite, α-hydroxymetoprolol, were measured over 1 dosing interval in women treated with metoprolol (25-750 mg/day) during early pregnancy (n = 4), mid-pregnancy (n = 14), and late pregnancy (n = 15), as well as postpartum (n = 9) with (n = 4) and without (n = 5) lactation. Subjects were genotyped for CYP2D6 loss-of-function allelic variants. Using paired analysis, mean metoprolol apparent oral clearance was significantly higher in mid-pregnancy (361 ± 223 L/h, n = 5, P < .05) and late pregnancy (568 ± 273 L/h, n = 8, P < .05) compared with ≥3 months postpartum (200 ± 131 and 192 ± 98 L/h, respectively). When the comparison was limited to extensive metabolizers (EMs), metoprolol apparent oral clearance was significantly higher during both mid- and late pregnancy (P < .05). Relative infant exposure to metoprolol through breast milk was <1.0% of maternal weight-adjusted dose (n = 3). Because of the large, pregnancy-induced changes in metoprolol pharmacokinetics, if inadequate clinical responses are encountered, clinicians who prescribe metoprolol during pregnancy should be prepared to make aggressive changes in dosage (dose and frequency) or consider using an alternate beta-blocker.
authors.affiliation: Department of Pharmacy, University of Washington, Seattle, WA, USA.
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Ryu
authors.affiliation: Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Sara
authors.initials: S
authors.lastname: Eyal
authors.affiliation: Department of Pharmacy, University of Washington, Seattle, WA, USA.|Department of Obstetrics & Gynecology, University of Washington, Seattle, WA, USA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Easterling
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Steve N
authors.initials: SN
authors.lastname: Caritis
authors.affiliation: School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.|School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Raman
authors.initials: R
authors.lastname: Venkataraman
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Hankins
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Rytting
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, WA, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Thummel
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, WA, USA.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Kelly
authors.affiliation: Department of Pharmacy, University of Washington, Seattle, WA, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Risler
authors.affiliation: Department of Pharmacy, University of Washington, Seattle, WA, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Phillips
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, WA, USA.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Honaker
authors.affiliation: Department of Pharmacy, University of Washington, Seattle, WA, USA.|Department of Pharmaceutics, University of Washington, Seattle, WA, USA.
authors.forename: Danny D
authors.initials: DD
authors.lastname: Shen
authors.affiliation: Department of Pharmacy, University of Washington, Seattle, WA, USA.|Department of Obstetrics & Gynecology, University of Washington, Seattle, WA, USA.
authors.forename: Mary F
authors.initials: MF
authors.lastname: Hebert
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000328:Adult; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics; D005260:Female; D005838:Genotype; D006801:Humans; D007774:Lactation / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D008790:Metoprolol / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008895:Milk, Human / Q000378:metabolism; D049590:Postpartum Period / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000652:urine; D011247:Pregnancy / Q000097:blood / Q000378:metabolism* / Q000652:urine; D055815:Young Adult
chemical_list: D000319:Adrenergic beta-Antagonists; D003692:Delayed-Action Preparations; D019389:Cytochrome P-450 CYP2D6; D008790:Metoprolol
keywords: CYP2D6; breast milk; hypertension; metoprolol; pharmacokinetics; pregnancy