Development and Validation of Physiologically Based Pharmacokinetic Model of Levetiracetam to Predict Exposure and Dose Optimization in Pediatrics

Shao, Wenxin; Shen, Chaozhuang; Wang, Wenhui; Sun, Hua; Wang, Xiaohu; Geng, Kuo; Wang, Xingwen; Xie, Haitang

doi:10.1016/j.xphs.2023.03.025

Cited by 10 publications

(2 citation statements)

References 37 publications

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“…It has been used to justify a biowaiver for a selected BCS 2 compounds [124] and determine the impact of different formulation factors such as solubility, particle size, size distribution, and food on the absorption of drugs [125][126][127][128][129][130][131]. The ADAM model is also available commercially, Symcyp®, and is used to predict the effect of drug release rate on the absorption [120,[132][133][134], to allow the optimization of paediatric drug [135,136], and to investigate drug-drug interactions [137]. Additional compartmental models are reviewed in Huang et al [4].…”

Section: Compartmental Modelsmentioning

confidence: 99%

Advances in Modeling Approaches for Oral Drug Delivery: Artificial Intelligence, Physiologically Based Pharmacokinetic, and First-Principal Models

Arav

2024

Preprint

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Oral drug absorption is the primary route for drug administration. However, this process hinges on multiple factors, including the drug’s physicochemical properties, formulation characteristics, and gastrointestinal physiology. Given its intricacy and the exorbitant costs associated with experimentation, the trial-and-error method proves prohibitively expensive. Theoretical models have emerged as a cost-effective alternative by assimilating data from diverse experiments and theoretical considerations. These models fall into three categories: data-driven models, encompassing classical pharmacokinetics, quantitative-structure models (QSAR), and machine/deep learning. Mechanism-based models include quasi-equilibrium, steady-state, and physiologically based pharmacokinetics, alongside first principles such as molecular dynamics and continuum models. This review provides an overview of recent modeling endeavors across these categories, evaluating their respective advantages and limitations. Additionally, a primer on partial differential equations and their numerical solutions is included in the supplementary materials, recognizing their utility in modeling physiological systems despite their mathematical complexity limiting their widespread application in this field.

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Section: Compartmental Modelsmentioning

confidence: 99%

Advances in Modeling Approaches for Oral Drug Delivery: Artificial Intelligence, Physiologically Based Pharmacokinetic, and First-Principal Models

Arav

2024

Preprint

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“…Examples of such subpopulations include pregnant and lactating women, fetuses, neonates and infants, and other pediatric groups [2][3][4]. A major cornerstone of PBPK modeling is the incorporation of unique patient physiology, and it is thus a powerful tool for anticipating how drug PK could differ in these populations compared to populations more extensively studied [5][6][7]. Additionally, this tool can be used for in silico predictions aimed at the rational choosing of "first in population" doses for these patients, when traditional allometric scaling may be less accurate.…”

Section: Introductionmentioning

confidence: 99%

Physiologically Based Pharmacokinetics Modeling in the Neonatal Population—Current Advances, Challenges, and Opportunities

Dinh,

Johnson,

Grimstein

et al. 2023

Pharmaceutics

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Physiologically based pharmacokinetic (PBPK) modeling is an approach to predicting drug pharmacokinetics, using knowledge of the human physiology involved and drug physiochemical properties. This approach is useful when predicting drug pharmacokinetics in under-studied populations, such as pediatrics. PBPK modeling is a particularly important tool for dose optimization for the neonatal population, given that clinical trials rarely include this patient population. However, important knowledge gaps exist for neonates, resulting in uncertainty with the model predictions. This review aims to outline the sources of variability that should be considered with developing a neonatal PBPK model, the data that are currently available for the neonatal ontogeny, and lastly to highlight the data gaps where further research would be needed.

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SIL‐IS LC–ESI–MS/MS method for simultaneous quick detection of amoxicillin and clavulanic acid in human plasma: Development, validation and its application to a pharmacokinetics study

Wu,

Wang,

Zhang

et al. 2024

Biomedical Chromatography

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A liquid chromatography electrospray ionization tandem mass spectrometry method with amoxicillin‐d4 as the stable isotope‐labeled internal standard for simultaneous quick detection of amoxicillin and clavulanic acid in human plasma was developed and validated. Chromatographic separations were performed on a Hedera ODS‐2 column (2.1 × 150 mm, 5 μm). The mobile phases for gradient elution were aqueous solution containing 0.2% acetic acid (AA) (mobile phase A) together with organic phase solution (acetonitrile and methanol mixed solution, mobile phase B). Mass spectrometry was performed using negative electrospray ionization in multiple reaction monitoring mode. The target fragment ion pairs of amoxicillin, clavulanic acid and amoxicillin‐d4 were m/z 364.1 → 223.1, 198.1 → 135.9 and 368.1 → 227.1, respectively. The linear ranges of this method were 40–5,000 ng/ml for amoxicillin and 30–2,500 ng/ml for clavulanic acid, with coefficient of determination > 0.9900. This method validation included selectivity, standard curve, lower limit of quantitation, accuracy, precision, recovery, matrix effect (hemolytic matrix and hyperlipidemic matrix), carryover, stability, dilution reliability and incurred sample reanalysis study. A successful application of this method was realized in a pharmacokinetic study after administration of amoxicillin–clavulanic acid potassium granules.

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Development and Validation of Physiologically Based Pharmacokinetic Model of Levetiracetam to Predict Exposure and Dose Optimization in Pediatrics

Cited by 10 publications

References 37 publications

Advances in Modeling Approaches for Oral Drug Delivery: Artificial Intelligence, Physiologically Based Pharmacokinetic, and First-Principal Models

Advances in Modeling Approaches for Oral Drug Delivery: Artificial Intelligence, Physiologically Based Pharmacokinetic, and First-Principal Models

Physiologically Based Pharmacokinetics Modeling in the Neonatal Population—Current Advances, Challenges, and Opportunities

SIL‐IS LC–ESI–MS/MS method for simultaneous quick detection of amoxicillin and clavulanic acid in human plasma: Development, validation and its application to a pharmacokinetics study

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