Application of a physiologically based pharmacokinetic model to predict isoniazid disposition during pregnancy

Amaeze, Ogochukwu U.; Isoherranen, Nina

doi:10.1111/cts.13614

Cited by 3 publications

(1 citation statement)

References 48 publications

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“…PBPK modelling can also predict drug disposition during pregnancy. For instance, Amaeze et al [ 112 ] developed a PBPK model to evaluate N-acetyltransferase 2 phenotype-specific effects of pregnancy on isoniazid disposition. Hence, tailoring dosage strategies for vulnerable groups is increasingly becoming a reality.…”

Section: Pharmacometrics Tools: Significance and Challenges In Precis...mentioning

confidence: 99%

Advancing Precision Medicine: A Review of Innovative In Silico Approaches for Drug Development, Clinical Pharmacology and Personalized Healthcare

Marques,

Costa,

Pereira

et al. 2024

Pharmaceutics

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The landscape of medical treatments is undergoing a transformative shift. Precision medicine has ushered in a revolutionary era in healthcare by individualizing diagnostics and treatments according to each patient’s uniquely evolving health status. This groundbreaking method of tailoring disease prevention and treatment considers individual variations in genes, environments, and lifestyles. The goal of precision medicine is to target the “five rights”: the right patient, the right drug, the right time, the right dose, and the right route. In this pursuit, in silico techniques have emerged as an anchor, driving precision medicine forward and making this a realistic and promising avenue for personalized therapies. With the advancements in high-throughput DNA sequencing technologies, genomic data, including genetic variants and their interactions with each other and the environment, can be incorporated into clinical decision-making. Pharmacometrics, gathering pharmacokinetic (PK) and pharmacodynamic (PD) data, and mathematical models further contribute to drug optimization, drug behavior prediction, and drug–drug interaction identification. Digital health, wearables, and computational tools offer continuous monitoring and real-time data collection, enabling treatment adjustments. Furthermore, the incorporation of extensive datasets in computational tools, such as electronic health records (EHRs) and omics data, is also another pathway to acquire meaningful information in this field. Although they are fairly new, machine learning (ML) algorithms and artificial intelligence (AI) techniques are also resources researchers use to analyze big data and develop predictive models. This review explores the interplay of these multiple in silico approaches in advancing precision medicine and fostering individual healthcare. Despite intrinsic challenges, such as ethical considerations, data protection, and the need for more comprehensive research, this marks a new era of patient-centered healthcare. Innovative in silico techniques hold the potential to reshape the future of medicine for generations to come.

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Section: Pharmacometrics Tools: Significance and Challenges In Precis...mentioning

confidence: 99%

Advancing Precision Medicine: A Review of Innovative In Silico Approaches for Drug Development, Clinical Pharmacology and Personalized Healthcare

Marques,

Costa,

Pereira

et al. 2024

Pharmaceutics

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Precision Medicine Strategies to Improve Isoniazid Therapy in Patients with Tuberculosis

Thomas,

Raju,

Mallayasamy

et al. 2024

Eur J Drug Metab Pharmacokinet

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Due to interindividual variability in drug metabolism and pharmacokinetics, traditional isoniazid fixed-dose regimens may lead to suboptimal or toxic isoniazid concentrations in the plasma of patients with tuberculosis, contributing to adverse drug reactions, therapeutic failure, or the development of drug resistance. Achieving precision therapy for isoniazid requires a multifaceted approach that could integrate various clinical and genomic factors to tailor the isoniazid dose to individual patient characteristics. This includes leveraging molecular diagnostics to perform the comprehensive profiling of host pharmacogenomics to determine how it affects isoniazid metabolism, such as its metabolism by N -acetyltransferase 2 (NAT2), and studying drug-resistant mutations in the Mycobacterium tuberculosis genome for enabling targeted therapy selection. Several other molecular signatures identified from the host pharmacogenomics as well as other omics-based approaches such as gut microbiome, epigenomic, proteomic, metabolomic, and lipidomic approaches have provided mechanistic explanations for isoniazid pharmacokinetic variability and/or adverse drug reactions and thereby may facilitate precision therapy of isoniazid, though further validations in larger and diverse populations with tuberculosis are required for clinical applications. Therapeutic drug monitoring and population pharmacokinetic approaches allow for the adjustment of isoniazid dosages based on patient-specific pharmacokinetic profiles, optimizing drug exposure while minimizing toxicity and the risk of resistance. Current evidence has shown that with the integration of the host pharmacogenomics—particularly NAT2 and Mycobacterium tuberculosis genomics data along with isoniazid pharmacokinetic concentrations in the blood and patient factors such as anthropometric measurements, comorbidities, and type and timing of food administered—precision therapy approaches in isoniazid therapy can be tailored to the specific characteristics of both the host and the pathogen for improving tuberculosis treatment outcomes. Supplementary Information The online version contains supplementary material available at 10.1007/s13318-024-00910-7.

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Pharmacokinetics and PBPK Models During Pregnancy, Lactation, and Developmental Stages

Lin,

Chen,

Fisher

2024

Reference Module in Biomedical Sciences

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Application of a physiologically based pharmacokinetic model to predict isoniazid disposition during pregnancy

Cited by 3 publications

References 48 publications

Advancing Precision Medicine: A Review of Innovative In Silico Approaches for Drug Development, Clinical Pharmacology and Personalized Healthcare

Advancing Precision Medicine: A Review of Innovative In Silico Approaches for Drug Development, Clinical Pharmacology and Personalized Healthcare

Precision Medicine Strategies to Improve Isoniazid Therapy in Patients with Tuberculosis

Pharmacokinetics and PBPK Models During Pregnancy, Lactation, and Developmental Stages

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