Physiologically-based pharmacokinetic models to predict drug exposure during pregnancy

Ait-Chikh, Celia; Page, Guylène; Thoreau, Vincent

doi:10.1016/j.pharma.2023.09.005

Cited by 2 publications

(1 citation statement)

References 42 publications

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“…This allows the inclusion of prior gestational age-related changes in physiological parameters together with information on the physicochemical properties, in vitro disposition information (binding, metabolism, permeability, solubility, etc. ), and human PK of the drug to be considered in the PBPK model [ 1 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

An Application of a Physiologically Based Pharmacokinetic Approach to Predict Ceftazidime Pharmacokinetics in a Pregnant Population

Abduljalil,

Gardner,

Jamei

2024

Pharmaceutics

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Physiological changes during pregnancy can alter maternal and fetal drug exposure. The objective of this work was to predict maternal and umbilical ceftazidime pharmacokinetics during pregnancy. Ceftazidime transplacental permeability was predicted from its physicochemical properties and incorporated into the model. Predicted concentrations and parameters from the PBPK model were compared to the observed data. PBPK predicted ceftazidime concentrations in non-pregnant and pregnant subjects of different gestational weeks were within 2-fold of the observations, and the observed concentrations fell within the 5th–95th prediction interval from the PBPK simulations. The calculated transplacental clearance (0.00137 L/h/mL of placenta volume) predicted an average umbilical cord-to-maternal plasma ratio of 0.7 after the first dose, increasing to about 1.0 at a steady state, which also agrees well with clinical observations. The developed maternal PBPK model adequately predicted the observed exposure and kinetics of ceftazidime in the pregnant population. Using a verified population-based PBPK model provides valuable insights into the disposition of drug concentrations in special individuals that are otherwise difficult to study and, in addition, offers the possibility of supplementing sparse samples obtained in vulnerable populations with additional knowledge, informing the dosing adjustment and study design, and improving the efficacy and safety of drugs in target populations.

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Section: Introductionmentioning

confidence: 99%

An Application of a Physiologically Based Pharmacokinetic Approach to Predict Ceftazidime Pharmacokinetics in a Pregnant Population

Abduljalil,

Gardner,

Jamei

2024

Pharmaceutics

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Dose Optimization Informed by PBPK Modeling: State‐of‐the Art and Future

Rowland Yeo,

Gil Berglund,

Chen

2024

Clin Pharma and Therapeutics

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Model‐informed drug development (MIDD) is a powerful quantitative approach that plays an integral role in drug development and regulatory review. While applied throughout the life cycle of the development of new drugs, a key application of MIDD is to inform clinical trial design including dose selection and optimization. To date, physiologically‐based pharmacokinetic (PBPK) modeling, an established component of the MIDD toolkit, has mainly been used for assessment of drug–drug interactions (DDIs) and consequential dose adjustments in regulatory submissions. As a result of recent scientific advances and growing confidence in the utility of the approach, PBPK models are being increasingly applied to provide dose recommendations for subjects with differing ages, genetics, and disease states. In this review, we present our perspective on the current landscape of regulatory acceptance of PBPK applications supported by relevant case studies. We also discuss the recent progress and future challenges associated with expanding the utility of PBPK models into emerging areas for regulatory decision making, especially dose optimization in highly vulnerable and understudied populations and facilitating diversity in clinical trials.

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Physiologically-based pharmacokinetic models to predict drug exposure during pregnancy

Cited by 2 publications

References 42 publications

An Application of a Physiologically Based Pharmacokinetic Approach to Predict Ceftazidime Pharmacokinetics in a Pregnant Population

An Application of a Physiologically Based Pharmacokinetic Approach to Predict Ceftazidime Pharmacokinetics in a Pregnant Population

Dose Optimization Informed by PBPK Modeling: State‐of‐the Art and Future

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