ArticlePharmaceutics2023
Total and Free Blood and Plasma Concentration Changes in Pregnancy for Medicines Highly Bound to Plasma Proteins: Application of Physiologically Based Pharmacokinetic Modelling to Understand the Impact on Efficacy.
Article in Pharmaceutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 8 citations in OpenAlex.
- Pharmacokinetics of Efavirenz in Pregnancy and Postpartum with and Without First-line Tuberculosis Drugs: Results from IMPAACT P1026s.Clinical pharmacokinetics · 2026Article
- Modelling the tail-phase pharmacokinetics of long-acting cabotegravir and rilpivirine from early pregnancy to postpartum at steady state.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- PBPK Models for Fetal Drug Exposure: A Critical Assessment of Current Approaches and Regulatory Readiness.Journal of clinical pharmacology · 2026Review
- Tacrolimus exposure during pregnancy in kidney and liver transplantation recipients: A comparison between whole blood and plasma concentration-to-dose ratios.British journal of clinical pharmacology · 2026Article
- PBPK modeling predicts rilzabrutinib dose adjustments using BTK occupancy for CYP3A4 interactions and hepatic impairment.Scientific reports · 2026Article
- Physiologically-Based Pharmacokinetic Modeling to Investigate Piperaquine Exposure in Pregnant Women Using an Individualized Profile Approach.Clinical and translational science · 2026Article
- A review of immunosuppressive therapy in the context of uterine VCA and pregnancy.Frontiers in transplantation · 2026Review
- Application of Physiologically Based Pharmacokinetic Modeling in the Research of Anti-HIV Drugs.Current drug metabolism · 2025Review
- Advances in Psychotropic Treatment for Pregnant Women: Efficacy, Adverse Outcomes, and Therapeutic Monitoring.Journal of clinical medicine · 2024Review
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Free drug concentrations are generally considered the pharmacologically active moiety and are important for cellular diffusion and distribution. Pregnancy-related changes in plasma protein binding and blood partitioning are due to decreases in plasma albumin, alpha-1-acid glycoprotein, and haematocrit; this may lead to increased free concentrations, tissue distribution, and clearance during pregnancy. In this paper we highlight the importance and challenges of considering changes in total and free concentrations during pregnancy. For medicines highly bound to plasma proteins, such as tacrolimus, efavirenz, clindamycin, phenytoin, and carbamazepine, differential changes in concentrations of free drug during pregnancy may be clinically significant and have important implications for dose adjustment. Therapeutic drug monitoring usually relies on the measurement of total concentrations; this can result in dose adjustments that are not necessary when changes in free concentrations are considered. We explore the potential of physiologically based pharmacokinetic (PBPK) models to support the understanding of the changes in plasma proteins binding, using tacrolimus and efavirenz as example drug models. The exposure to either drug was predicted to be reduced during pregnancy; however, the decrease in the exposure to the total tacrolimus and efavirenz were significantly larger than the reduction in the exposure to the free drug. These data show that PBPK modelling can support the impact of the changes in plasma protein binding and may be used for the simulation of free concentrations in pregnancy to support dosing decisions.
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