Pharmacometrics in pregnancy: An unmet need

Alice Ban Ke, Amin Rostami-Hodjegan, Ping Zhao, Jashvant D. Unadkat

    Research output: Contribution to journalArticlepeer-review


    Pregnant women and their fetuses are orphan populations with respect to the safety and efficacy of drugs. Physiological and absorption, distribution, metabolism, and excretion (ADME) changes during pregnancy can significantly affect drug pharmacokinetics (PK) and may necessitate dose adjustment. Here, the specific aspects related to the design, execution, and analysis of clinical studies in pregnant women are discussed, underlining the unmet need for top-down pharmacometrics analyses and bottom-up modeling approaches. The modeling tools that support data analysis for the pregnancy population are reviewed, with a focus on physiologically based pharmacokinetics (PBPK) and population pharmacokinetics (POP-PK). By integrating physiological data, preclinical data, and clinical data (e.g., via POP-PK) to quantify anticipated changes in the PK of drugs during pregnancy, the PBPK approach allows extrapolation beyond the previously studied model drugs to other drugs with well-characterized ADME characteristics. Such a systems pharmacology approach can identify drugs whose PK may be altered during pregnancy, guide rational PK study design, and support dose adjustment for pregnant women. © 2014 by Annual Reviews.
    Original languageEnglish
    Pages (from-to)53-69
    Number of pages16
    JournalAnnual Review of Pharmacology and Toxicology
    Publication statusPublished - 2014


    • CYP
    • Modeling
    • PBPK
    • POP-PK
    • Simulation


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