Anatomical, Physiological and Metabolic Changes with Gestational Age during Normal Pregnancy: A Database for Parameters Required in Physiologically Based Pharmacokinetic Modelling
Abstract
Background Pregnancy is associated with considerable changes in the physiological, anatomical and biochemical attributes in women. These may alter the exposure to xenobiotics between pregnant and non-pregnant women who receive similar doses, with implications for different susceptibility to environmental pollutants or therapeutic agents. Physiologically based pharmacokinetic (PBPK) models together with in vitro in vivo extrapolation (IVIVE) of absorption, distribution, metabolism and excretion (ADME) characteristics may capture the likely changes. However, such models require comprehensive information on the longitudinal variations of PBPK parameter values; a set of data that are as yet not available from a singular source. Aim The aim of this article was to collect, integrate and analyse the available time-variant parameters that are needed for the PBPK modelling of xenobiotic kinetics in a healthy pregnant population. Methods A structured literature search was carried out on anatomical, physiological and biochemical parameters likely to change in pregnancy and alter the kinetics of xenobiotics. Collated data were carefully assessed, integrated and analysed for trends with gestational age. Algorithms were generated to describe the changes in parameter values with gestational age. These included changes in maternal weight, the individual organ volumes and blood flows, glomerular filtration rates, and some drug-metabolising enzyme activities. Results Articles were identified u…
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A systematic literature summary catalogued 35 pregnancy-related anatomical, physiological and biochemical parameters relevant to p-PBPK models that should be considered.
“A systematic summary of literature to catalogue pregnancy-related anatomical, physiological and biochemical changes of relevance to p-PBPK models listed 35 different parameters that should be taken into consideration (Abduljalil et al., 2012).”
From Pregnancy-related maternal physiological adaptations and fetal chemical exposure (2023) · cites this paper as Abduljalil et al., 2012
The 35 parameters range from changes in organ size, blood volume and flow to plasma lipids, metabolic enzyme activities, and hormonal changes.
“These ranged from changes in organ size and blood volume and flow to plasma lipids, metabolic enzyme activities, and hormonal changes in line with the many significant changes known to take place in pregnancy (Fig. 1).”
From Pregnancy-related maternal physiological adaptations and fetal chemical exposure (2023) · cites this paper as Abduljalil et al., 2012
The systematic summary presented normal ranges of these parameters across normal pregnancy, excluding women with pregnancy-related complications or conditions.
“The ambitious work also presented the normal range of these parameters across normal pregnancy, excluding women with any pregnancy-related complications or conditions (Abduljalil et al., 2012).”
From Pregnancy-related maternal physiological adaptations and fetal chemical exposure (2023) · cites this paper as Abduljalil et al., 2012
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- Authors
- Abduljalil, K., Furness, P., Johnson, T. N., Rostami-Hodjegan, A., & Soltani, H.
- Affiliations
- Simcyp (United Kingdom) (GB)
- Sheffield Hallam University (GB)
- Corresponding author
- Abduljalil, Khaled
- Venue
- Clinical Pharmacokinetics
- Published
- 2012-06
- Volume
- 51
- Issue
- 6
- Pages
- 365-396
- ISSN
- 0312-5963 (ISSN-L)
- OpenAlex
- W2225273737
- Cited by
- 371
- References
- 382
- Citations by year
- 2026: 22 · 2025: 31 · 2024: 40 · 2023: 34 · 2022: 30 · 2021: 30 · 2020: 31 · 2019: 29 · 2018: 23 · 2017: 22 · 2016: 17 · 2015: 16 · 2014: 20 · 2013: 16 · 2012: 8
- FWCI
- 18.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Pharmacokinetics (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- SHURA (Sheffield Hallam University Research Archive) (Sheffield Hallam University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Keywords
- pregnancy, gestational age, physiological changes in pregnancy, physiologically based pharmacokinetic modeling, time-varying parameters, organ volume, cardiac output, glomerular filtration rate, drug-metabolizing enzymes, protein binding, maternal weight
- MeSH terms
- Algorithms, Body Weight, Female, Gestational Age, Glomerular Filtration Rate, Humans, Inactivation, Metabolic, Models, Biological, Organ Size, Pregnancy, Reference Values, Regional Blood Flow, Xenobiotics, Databases, Factual
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