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.

Methods and Findings

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.

Conclusion

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.

Abstract

Shinya Ito and colleagues systematically review the literature to identify research reporting medications reporting pregnancy-associated changes in pharmacokinetics.

Author Summary

Why Was This Study Done

• Pregnant women take a variety of medications, including prescription and over-the-counter medications, with an estimated prevalence of greater than 90%.

• Some studies have demonstrated significant changes in pharmacokinetics (absorption, distribution, metabolism, and excretion of drugs) during pregnancy and resultant clinical impact, but others have not, which calls for critical assessment of the evidence.

What Did the Researchers Do and Find?

• We conducted a systematic review, and identified 198 studies, involving 121 different medications, that fulfilled the inclusion criteria.

• Decrease in drug exposure mainly due to increased elimination was frequently observed across the drug classes.

• There is a lack of studies describing changes in clinical outcomes, or the lack thereof, associated with altered pharmacokinetics during pregnancy.

What Do These Findings Mean?

• A significant gap exists between our knowledge of pharmacokinetic changes in pregnancy and their clinical consequences.

• It is essential for clinicians to be aware of these pregnancy-related changes in pharmacokinetics, and to critically examine their potential clinical implications.