title: Pregnancy-Associated Changes in Pharmacokinetics: A Systematic Review.
abstract: BACKGROUND
  Women are commonly prescribed a variety of medications during pregnancy. As most organ systems are affected by the substantial anatomical and physiological changes that occur during pregnancy, it is expected that pharmacokinetics (PK) (absorption, distribution, metabolism, and excretion of drugs) would also be affected in ways that may necessitate changes in dosing schedules. The objective of this study was to systematically identify existing clinically relevant evidence on PK changes during pregnancy.
  
  
  RESULTS
  Systematic searches were conducted in MEDLINE (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (Ovid), and Web of Science (Thomson Reuters), from database inception to August 31, 2015. An update of the search from September 1, 2015, to May 20, 2016, was performed, and relevant data were added to the present review. No language or date restrictions were applied. All publications of clinical PK studies involving a group of pregnant women with a comparison to nonpregnant participants or nonpregnant population data were eligible to be included in this review. A total of 198 studies involving 121 different medications fulfilled the inclusion criteria. In these studies, commonly investigated drug classes included antiretrovirals (54 studies), antiepileptic drugs (27 studies), antibiotics (23 studies), antimalarial drugs (22 studies), and cardiovascular drugs (17 studies). Overall, pregnancy-associated changes in PK parameters were often observed as consistent findings among many studies, particularly enhanced drug elimination and decreased exposure to total drugs (bound and unbound to plasma proteins) at a given dose. However, associated alterations in clinical responses and outcomes, or lack thereof, remain largely unknown.
  
  
  CONCLUSIONS
  This systematic review of pregnancy-associated PK changes identifies a significant gap between the accumulating knowledge of PK changes in pregnant women and our understanding of their clinical impact for both mother and fetus. It is essential for clinicians to be aware of these unique pregnancy-related changes in PK, and to critically examine their clinical implications.
authors: Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Gali
authors: http://orcid.org/0000-0001-6484-3769
authors: G
authors: Pariente
authors: Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Tom
authors: T
authors: Leibson
authors: Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Alexandra
authors: A
authors: Carls
authors: Hospital Library, Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Thomasin
authors: http://orcid.org/0000-0003-4623-7225
authors: T
authors: Adams-Webber
authors: Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Ontario, Canada.|Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.|Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.|Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada.
authors: Shinya
authors: S
authors: Ito
authors: Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
authors: Gideon
authors: G
authors: Koren
mesh_terms: D005260:Female; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D011247:Pregnancy
chemical_list: D004364:Pharmaceutical Preparations