Transplacental Passage of Acetaminophen in Term Pregnancy.
ObjectiveThe objective of this study was to determine the maternal and fetal pharmacokinetic (PK) profiles of acetaminophen after administration of a therapeutic oral dose.Study DesignAfter obtaining Institutional Review Board approval and their written informed consent, pregnant women were given a single oral dose (1,000 mg) of acetaminophen upon admission for scheduled cesarean delivery. Maternal venous blood and fetal cord blood were obtained at the time of delivery and acetaminophen levels were measured using gas chromatography-mass spectroscopy. PK parameters were calculated by noncompartmental analysis. Nonparametric correlation of maternal/fetal acetaminophen levels and PK curves were calculated.ResultsIn this study, 34 subjects were enrolled (median, 32 years; range, 25-39 years). The median maternal weight was 82 kg (range, 62-100 kg). All but two subjects were delivered beyond 39 weeks' gestation. The median newborn birth weight was 3,590 g (interquartile range, 3,403-3,848 g). Noncompartmental analysis described similar PK parameters in the maternal (T1/2, 84 minutes; apparent clearance [Cl/F], 28.8 L/h; apparent volume of distribution [Vd/F], 57.5 L) and fetal compartments (T1/2, 82 minutes; Cl/F, 31.2 L/h; Vd/F, 61.2 L). Paired maternal/fetal acetaminophen levels were highly correlated (p< 0.0001).ConclusionFetal acetaminophen PKs in the fetus parallels that in the mother suggesting that placental transfer is flow limited. Maternal acetaminophen levels can be used as a surrogate for fetal exposure.
Department of Maternal-Fetal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
Joshua F
JF
Nitsche
Department of Maternal-Fetal Medicine and Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana.
Avinash S
AS
Patil
Department of Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota.
Loralie J
LJ
Langman
Department of Neonatology, Mayo Clinic College of Medicine, Rochester, Minnesota.
Hannah J
HJ
Penn
Department of Neonatology, Mayo Clinic College of Medicine, Rochester, Minnesota.
Douglas
D
Derleth
Department of Maternal-Fetal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota.
William J
WJ
Watson
Department of Maternal-Fetal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota.
Brian C
BC
Brost
D000082:Acetaminophen / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D000328:Adult; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D005865:Gestational Age; D006801:Humans; D016014:Linear Models; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011263:Pregnancy Trimester, Third / Q000097:blood*; D011295:Prenatal Care; D011446:Prospective Studies; D047929:Term Birth
D000082:Acetaminophen