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Am J Perinatol 2017; 34(06): 541-543
DOI: 10.1055/s-0036-1593845
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Transplacental Passage of Acetaminophen in Term Pregnancy

Joshua F. Nitsche
1   Department of Maternal–Fetal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina
,
Avinash S. Patil
2   Department of Maternal–Fetal Medicine and Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana
,
Loralie J. Langman
3   Department of Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota
,
Hannah J. Penn
4   Department of Neonatology, Mayo Clinic College of Medicine, Rochester, Minnesota
,
Douglas Derleth
4   Department of Neonatology, Mayo Clinic College of Medicine, Rochester, Minnesota
,
William J. Watson
5   Department of Maternal–Fetal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota
,
Brian C. Brost
5   Department of Maternal–Fetal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota
› Author Affiliations
Further Information

Publication History

19 June 2016

22 September 2016

Publication Date:
02 November 2016 (online)

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Abstract

Objective The objective of this study was to determine the maternal and fetal pharmacokinetic (PK) profiles of acetaminophen after administration of a therapeutic oral dose.

Study Design After 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.

Results In 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 (T 1/2, 84 minutes; apparent clearance [Cl/F], 28.8 L/h; apparent volume of distribution [Vd/F], 57.5 L) and fetal compartments (T 1/2, 82 minutes; Cl/F, 31.2 L/h; Vd/F, 61.2 L). Paired maternal/fetal acetaminophen levels were highly correlated (p < 0.0001).

Conclusion Fetal 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.

Keywords

fetal drug exposure - acetaminophen - pregnancy - pharmacokinetics
 

  • References

  • 1 Werler MM, Mitchell AA, Hernandez-Diaz S, Honein MA. Use of over-the-counter medications during pregnancy. Am J Obstet Gynecol 2005; 193 (3 Pt 1): 771-777
    CrossrefPubMedGoogle Scholar
  • 2 Liew Z, Ritz B, Rebordosa C, Lee PC, Olsen J. Acetaminophen use during pregnancy, behavioral problems, and hyperkinetic disorders. JAMA Pediatr 2014; 168 (4) 313-320
    CrossrefPubMedGoogle Scholar
  • 3 Haibach H, Akhter JE, Muscato MS, Cary PL, Hoffmann MF. Acetaminophen overdose with fetal demise. Am J Clin Pathol 1984; 82 (2) 240-242
    CrossrefPubMedGoogle Scholar
  • 4 Eyers S, Weatherall M, Jefferies S, Beasley R. Paracetamol in pregnancy and the risk of wheezing in offspring: a systematic review and meta-analysis. Clin Exp Allergy 2011; 41 (4) 482-489
    CrossrefPubMedGoogle Scholar
  • 5 Wang PH, Yang MJ, Lee WL, Chao HT, Yang ML, Hung JH. Acetaminophen poisoning in late pregnancy. A case report. J Reprod Med 1997; 42 (6) 367-371
    PubMedGoogle Scholar
  • 6 Levy G, Garrettson LK, Soda DM. Letter: evidence of placental transfer of acetaminophen. Pediatrics 1975; 55 (6) 895–895
    PubMedGoogle Scholar
  • 7 Byer AJ, Traylor TR, Semmer JR. Acetaminophen overdose in the third trimester of pregnancy. JAMA 1982; 247 (22) 3114-3115
    CrossrefPubMedGoogle Scholar
  • 8 Ludmir J, Main DM, Landon MB, Gabbe SG. Maternal acetaminophen overdose at 15 weeks of gestation. Obstet Gynecol 1986; 67 (5) 750-751
    CrossrefPubMedGoogle Scholar
  • 9 Rosevear SK, Hope PL. Favourable neonatal outcome following maternal paracetamol overdose and severe fetal distress. Case report. Br J Obstet Gynaecol 1989; 96 (4) 491-493
    CrossrefPubMedGoogle Scholar
  • 10 Stokes IM. Paracetamol overdose in the second trimester of pregnancy. Case report. Br J Obstet Gynaecol 1984; 91 (3) 286-288
    CrossrefPubMedGoogle Scholar
  • 11 Briggs G, Freeman R, Yaffe S , eds. Drugs in Pregnancy and Lactation, 6 ed. Philadelphia: Lippincott Williams & Wilkins; 2002
    Google Scholar
  • 12 Tylenol professional product information. In: McNeil Consumer Healthcare; 2010
    PubMedGoogle Scholar
  • 13 Rayburn W, Wible-Kant J, Bledsoe P. Changing trends in drug use during pregnancy. J Reprod Med 1982; 27 (9) 569-575
    PubMedGoogle Scholar
  • 14 Naga Rani MA, Joseph T, Narayanan R. Placental transfer of paracetamol. J Indian Med Assoc 1989; 87 (8) 182-183
    PubMedGoogle Scholar
  • 15 Kulo A, van Calsteren K, Verbesselt R , et al. The impact of caesarean delivery on paracetamol and ketorolac pharmacokinetics: a paired analysis. J Biomed Biotechnol 2012; 2012: 437639 . Doi: 10.1155/2012/437639
    PubMedGoogle Scholar
  • 16 Mazaleuskaya LL, Sangkuhl K, Thorn CF, FitzGerald GA, Altman RB, Klein TE. PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics 2015; 25 (8) 416-426
    CrossrefPubMedGoogle Scholar