Abstract
Physiologically-based pharmacokinetics (PBPK) modeling is a robust tool that supports drug development and the pharmaceutical industry and regulatory authorities. Implementation of predictive systems in the clinics is more than ever a reality, resulting in a surge of interest for PBPK models by clinicians. We aimed to establish a repository of available PBPK models developed to date to predict drug-drug interactions (DDIs) in the different therapeutic areas by integrating intrinsic and extrinsic factors such as genetic polymorphisms of the cytochromes or environmental clues. This work includes peer-reviewed publications and models developed in the literature from October 2017 to January 2021. Information about the software, type of model, size, and population model was extracted for each article. In general, modeling was mainly done for DDI prediction via Simcyp® software and Full PBPK. Overall, the necessary physiological and physio-pathological parameters, such as weight, BMI, liver or kidney function, relative to the drug absorption, distribution, metabolism, and elimination and to the population studied for model construction was publicly available. Of the 46 articles, 32 sensibly predicted DDI potentials, but only 23% integrated the genetic aspect to the developed models. Marked differences in concentration time profiles and maximum plasma concentration could be explained by the significant precision of the input parameters such as Tissue: plasma partition coefficients, protein abundance, or Ki values. In conclusion, the models show a good correlation between the predicted and observed plasma concentration values. These correlations are all the more pronounced as the model is rich in data representative of the population and the molecule in question. PBPK for DDI prediction is a promising approach in clinical, and harmonization of clearance prediction may be helped by a consensus on selecting the best data to use for PBPK model development.
Highlights
In more cases than expected, the therapeutical management process involves a myriad of errors making drug-related problems (DRP) a recurring reviewed subject
Current treatment regimens rely on the anticipated relationship between drug doses, plasma levels, and desired effect
This review provides an overview of physiologically based pharmacokinetic (PBPK) model development and its integration into the application for PK predictions and decision-making tools
Summary
In more cases than expected, the therapeutical management process involves a myriad of errors making drug-related problems (DRP) a recurring reviewed subject. A large part of the DRP originates from drug prescribing issues (Perry et al, 2020). Difficulties can range from prescribing an inaccurate dose to inadequate administration frequency on top of a known allergy or a drug-drug interaction (DDIs). Among these risk factors, belonging to extremes of age, renal and liver impairment, or having genetic variations, are likely to increase developing DDI. Combination therapy is becoming increasingly prevalent in managing concurrent or single disease (Bi et al, 2018b), especially in geriatric patients. Dechanont et al showed that DDI represents 1.1% of overall hospital admissions in this population and that 22.2% of ADRs are related to DDIs
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