Emerging Strategies in Drug Development and Clinical Care in the Era of Personalized and Precision Medicine, 2nd Edition

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Clinical Pharmaceutics".

Deadline for manuscript submissions: closed (30 September 2024) | Viewed by 2028

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Special Issue Information

Dear Colleagues,

Modern medicine is going through an extremely important moment in its evolution in relation to the disease–drug–patient axis, gradually progressing from pure drug development, which initiates from the need to prevent or treat certain diseases, to the expansion of coherent therapeutic strategies which are personalized for each individual, in recognition of the fact that each patient is a distinct physio-pathological case. Remarkable advances in recent decades in the prevention strategies, diagnostic procedures and available treatments have paved the way to major improvements in patient care. Personalised medicine is approachable if comprehensive details are known about the pathogenesis; the therapeutic agents developed for the management of the pathology in question; the biochemical mechanisms of action of the drugs; the interactions of the drugs with each other and with other endogenous or exogenous factors; and the genetic and epigenetic background of the patient, their chronobiological, nutritional and socio-demographic characteristics.

In this framework, the aim of this Special Issue on “Emerging strategies in drug development and clinical care in the era of personalised and precision medicine” is to unify the most relevant papers addressing the state-of-the-art knowledge and future directions in drug development, therapeutic strategies, and innovative drug formulations, with a focus on biochemical mechanisms of action and drug design, as well as the relevant preclinical and clinical testing of efficacy, pharmacokinetics and toxicity in the era of precision and personalised medicine.

We welcome articles dealing with all aspects of pharmaceutical and medical care, from basic to clinical research, and invite scientists and drug specialists to publish their original research works, review articles, and communications on this wide health domain.

Dr. Cristina Manuela Drăgoi
Dr. Alina Crenguța Crenguţa Nicolae
Dr. Ion-Bogdan Bogdan Dumitrescu
Guest Editors

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Keywords

  • drug development
  • therapeutic strategies
  • preclinical and clinical drug research
  • drug design
  • drug–drug interactions
  • clinical care
  • toxicological studies
  • disease risk, disease prognosis and response to therapy
  • biomarkers identification and application
  • biochemistry of drug uptake, action, and metabolism
  • drug target discovery
  • individualized therapy
  • pharmacogenomics
  • novel therapeutics
  • non-drug-related health interferences
  • nutritional interventions
  • chronobiology
  • medicinal chemistry
  • phytochemicals
  • biologics
  • personalized medicine
  • precision medicine

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Published Papers (2 papers)

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Research

14 pages, 321 KiB  
Article
Genetic Variation in CYP2D6, UGT1A4, SLC6A2 and SLCO1B1 Alters the Pharmacokinetics and Safety of Mirabegron
by Paula Soria-Chacartegui, Patricia Cendoya-Ramiro, Eva González-Iglesias, Samuel Martín-Vílchez, Andrea Rodríguez-Lopez, Gina Mejía-Abril, Manuel Román, Sergio Luquero-Bueno, Dolores Ochoa and Francisco Abad-Santos
Pharmaceutics 2024, 16(8), 1077; https://doi.org/10.3390/pharmaceutics16081077 - 17 Aug 2024
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Abstract
Mirabegron is a drug used in overactive bladder (OAB) treatment. Genetic variation in pharmacogenes might alter its pharmacokinetics, affecting its efficacy and safety. This research aimed to analyze the impact of genetic variation on mirabegron pharmacokinetics and safety. Volunteers from three bioequivalence trials [...] Read more.
Mirabegron is a drug used in overactive bladder (OAB) treatment. Genetic variation in pharmacogenes might alter its pharmacokinetics, affecting its efficacy and safety. This research aimed to analyze the impact of genetic variation on mirabegron pharmacokinetics and safety. Volunteers from three bioequivalence trials (n = 79), treated with a single or a multiple dose of mirabegron 50 mg under fed or fasting conditions, were genotyped for 115 variants in pharmacogenes and their phenotypes were inferred. A statistical analysis was performed, searching for associations between genetics, pharmacokinetics and safety. CYP2D6 intermediate metabolizers showed a higher elimination half-life (t1/2) (univariate p-value (puv) = 0.018) and incidence of adverse reactions (ADRs) (puv = 0.008, multivariate p (pmv) = 0.010) than normal plus ultrarapid metabolizers. The UGT1A4 rs2011425 T/G genotype showed a higher t1/2 than the T/T genotype (puv = 0.002, pmv = 0.003). A lower dose/weight corrected area under the curve (AUC/DW) and higher clearance (CL/F) were observed in the SLC6A2 rs12708954 C/C genotype compared to the C/A genotype (puv = 0.015 and 0.016) and ADR incidence was higher when the SLCO1B1 function was decreased (puv = 0.007, pmv = 0.010). The lower elimination and higher ADR incidence when CYP2D6 activity is reduced suggest it might be a useful biomarker in mirabegron treatment. UGT1A4, SLC6A2 and SLCO1B1 might also be involved in mirabegron pharmacokinetics. Full article
18 pages, 2431 KiB  
Article
Novel Genetic Variants Explaining Severe Adverse Drug Events after Clinical Implementation of DPYD Genotype-Guided Therapy with Fluoropyrimidines: An Observational Study
by Xando Díaz-Villamarín, María Martínez-Pérez, María Teresa Nieto-Sánchez, Gabriela Ruiz-Tueros, Emilio Fernández-Varón, Alicia Torres-García, Beatriz González Astorga, Isabel Blancas, Antonio J. Iáñez, José Cabeza-Barrera and Rocío Morón
Pharmaceutics 2024, 16(7), 956; https://doi.org/10.3390/pharmaceutics16070956 - 19 Jul 2024
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Abstract
Fluoropyrimidines (FPs) are commonly prescribed in many cancer streams. The EMA and FDA-approved drug labels for FPs recommend genotyping the DPYD*2A (rs3918290), *13 (rs55886062), *HapB3 (rs56038477), alleles, and DPYD rs67376798 before treatment starts. We implemented the DPYD genotyping in our daily clinical [...] Read more.
Fluoropyrimidines (FPs) are commonly prescribed in many cancer streams. The EMA and FDA-approved drug labels for FPs recommend genotyping the DPYD*2A (rs3918290), *13 (rs55886062), *HapB3 (rs56038477), alleles, and DPYD rs67376798 before treatment starts. We implemented the DPYD genotyping in our daily clinical routine, but we still found patients showing severe adverse drug events (ADEs) to FPs. We studied among these patients the DPYD rs1801265, rs17376848, rs1801159, rs1801160, rs1801158, and rs2297595 as explanatory candidates of the interindividual differences for FP-related toxicities, examining the association with the response to FPs . We also studied the impact of DPYD testing for FP dose tailoring in our clinical practice and characterized the DPYD gene in our population. We found a total acceptance among physicians of therapeutic recommendations translated from the DPYD test, and this dose tailoring does not affect the treatment efficacy. We also found that the DPYD*4 (defined by rs1801158) allele is associated with a higher risk of ADEs (severity grade ≥ 3) in both the univariate (O.R. = 5.66; 95% C.I. = 1.35–23.67; p = 0.014) and multivariate analyses (O.R. = 5.73; 95% C.I. = 1.41–28.77; p = 0.019) among FP-treated patients based on the DPYD genotype. This makes it a candidate variant for implementation in clinical practice. Full article
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