Cocrystals by Design: A Rational Coformer Selection Approach for Tackling the API Problems

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(4), P. 1161 - 1161

Published: April 6, 2023

Active pharmaceutical ingredients (API) with unfavorable physicochemical properties and stability present a significant challenge during their processing into final dosage forms. Cocrystallization of such APIs suitable coformers is an efficient approach to mitigate the solubility concerns. A considerable number cocrystal-based products are currently being marketed show upward trend. However, improve API by cocrystallization, coformer selection plays paramount role. Selection not only improves drug's but also therapeutic effectiveness reduces side effects. Numerous have been used till date prepare pharmaceutically acceptable cocrystals. The carboxylic acid-based coformers, as fumaric acid, oxalic succinic citric most commonly in products. Carboxylic capable forming hydrogen bond contain smaller carbon chain APIs. This review summarizes role improving APIs, deeply explains utility afore-mentioned cocrystal formation. concludes brief discussion on patentability regulatory issues related

Language: Английский

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Fluorine in the pharmaceutical industry: Synthetic approaches and application of clinically approved fluorine-enriched anti-infectious medications

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 271, P. 116446 - 116446

Published: April 26, 2024

Language: Английский

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Pharmacogenetic Information on Drug Labels of the Italian Agency of Medicines (AIFA): Actionability and Comparison Across Other Regulatory Agencies

Clinical and Translational Science, Journal Year: 2025, Volume and Issue: 18(2)

Published: Feb. 1, 2025

ABSTRACT To plan future steps for the implementation and regulation of pharmacogenetic testing, any issue in management information by regulatory bodies must be identified. In this paper, an analysis summary product characteristics (SmCPs) drugs approved Italian Drug Agency (AIFA) was conducted. Among 4214 SmCPs 1063 active ingredients, 53.2% ( n = 2240) included at least one section, most frequently Anatomical Therapeutic Chemical category “Antineoplastic immunomodulatory agents”. contextualize these data international scenario, a level actionability, based on AIFA SmCPs, assigned to 608 drug/gene pairs FDA's “Table Pharmacogenomic Biomarkers Labels”, according PharmGKB (The Pharmacogenomics Knowledge Base). Approximately 67% were deemed classifiable: Based phrasing, half them genetic testing cataloged as “required” or “recommended” (mainly tumor somatic variants), whereas 40% “actionable” (mostly PK/PD‐related germline variants). The comparison with other agencies highlighted discordance levels actionability ranging from 1% 14%. This discrepancy may also point out need rethink language used AIFA‐approved clarify whether test is necessary not which subjects it has been recommended. For first time, detailed evaluation comparative presented, placing context laying groundwork rethinking indications SmCPs.

Language: Английский

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Pharmaceutical Cocrystals

Published: March 29, 2025

Language: Английский

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The Implementation of Pharmacogenetics in the United Kingdom

Handbook of experimental pharmacology, Journal Year: 2023, Volume and Issue: unknown, P. 3 - 32

Published: Jan. 1, 2023

Language: Английский

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Azathioprine dose tailoring based on pharmacogenetic information: Insights of clinical implementation

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 168, P. 115706 - 115706

Published: Oct. 17, 2023

Azathioprine is commonly used as an immunosuppressive antimetabolite in the treatment of acute lymphoblastic leukemia, autoimmune disorders (such Crohn's disease and rheumatoid arthritis), patients receiving organ transplants. Thiopurine-S-methyltransferase (TPMT) a cytoplasmic trans-methylase catalyzing S-methylation thiopurines. The active metabolites obtained from thiopurines are hydrolyzed into inactive forms by Nudix hydrolase 15 (NUDT15). TPMT*2 (defined rs1800462), *3A rs1800460 rs1142345), *3B rs1800460), *3C *6 rs75543815), NUDT15 rs116855232 genetic variant have been associated, with highest level evidence, response to azathioprine, and, approved drug label for azathioprine main pharmacogenetic dosing guidelines recommend starting reduced initial doses TPMT intermediate metabolizer (IM) considering alternative poor (PM) patients. This study aims assess clinical impact dose tailoring based on genotyping studying toxicity efficacy, starts, adjustments during follow-up, comparing IM/PM normal (NM) It also studied association tailored characterized TMPT variants our population. Results show that reduction IM (TPMT*1/*2, *1/*3A, or *1/*3C genotypes) related lower events compared NM (TPMT *1/*1 genotype), follow-up without showing differences efficacy. results support hypothesis existing other affecting toxicity.

Language: Английский

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Reshaping neuroimmunology: diagnosis and treatment in the era of precision medicine

Arquivos de Neuro-Psiquiatria, Journal Year: 2023, Volume and Issue: 81(12), P. 1125 - 1133

Published: Dec. 1, 2023

Abstract Precision medicine has revolutionized the field of neuroimmunology, with innovative approaches that characterize diseases based on their biology, deeper understanding factors leading to heterogeneity within same disease, development targeted therapies, and strategies tailor therapies each patient. This review explores impact precision various neuroimmunological conditions, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), optic neuritis, autoimmune encephalitis, immune-mediated neuropathies. We discuss advances in subtyping, recognition novel entities, promising biomarkers, more selective monoclonal antibodies cutting-edge synthetic cell-based immunotherapies disorders. In addition, we analyze challenges related affordability equity implementation these emerging technologies, especially situations limited resources.

Language: Английский

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Pharmacogenetics in Italy: current landscape and future prospects

Human Genomics, Journal Year: 2024, Volume and Issue: 18(1)

Published: July 10, 2024

Pharmacogenetics investigates sequence of genes that affect drug response, enabling personalized medication. This approach reduces drug-induced adverse reactions and improves clinical effectiveness, making it a crucial consideration for medical care. Numerous guidelines, drawn by global consortia scientific organizations, codify genotype-driven administration over 120 active substances. As the community acknowledges benefits genotype-tailored therapy traditionally agnostic administration, push its implementation into Italian healthcare system is gaining momentum. evolution influenced several factors, including improved access to patient genotypes, sequencing costs decrease, growing large-scale genetic studies, rising popularity direct-to-consumer pharmacogenetic tests, continuous improvement guidelines. Since EMA (European Medicines Agency) AIFA (Italian provide genotype information on leaflet without clear explicit indications gene testing, regulation testing pressing matter in Italy. In this manuscript, we have reviewed how overcome obstacles implementing practice system. Our particular emphasis has been germline given absence well-defined national directives contrast somatic pharmacogenetics.

Language: Английский

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Assessing heterogeneity of treatment effect in multiple sclerosis trials

Multiple Sclerosis Journal, Journal Year: 2023, Volume and Issue: 29(9), P. 1158 - 1161

Published: Aug. 1, 2023

Multiple sclerosis (MS) is heterogeneous with respect to outcomes, and evaluating possible heterogeneity of treatment effect (HTE) high interest. HTE non-random variation in the magnitude a on clinical outcome across levels covariate (i.e. patient attribute or set attributes). statistical techniques can evaluate HTE. The simplest but most bias-prone conventional one variable-at-a-time subgroup analysis. Recently, multivariable predictive approaches have been promoted provide more patient-centered results, by accounting for multiple relevant attributes simultaneously. We review used estimate trials MS.

Language: Английский

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Advancing pharmacogenetic testing in a tertiary hospital: a retrospective analysis after 10 years of activity

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 19, 2023

The field of pharmacogenetics (PGx) holds great promise in advancing personalized medicine by adapting treatments based on individual genetic profiles. Despite its benefits, there are still economic, ethical and institutional barriers that hinder implementation our healthcare environment. A retrospective analysis approach anonymized data sourced from electronic health records was performed, encompassing a diverse patient population evaluating key parameters such as prescribing patterns test results, to assess the impact pharmacogenetic testing. head-to-head comparison with previously published activity results within same laboratory also conducted contrast progress made after 10 years. revealed significant utilization testing daily clinical practice, 1,145 tests performed over 1-year period showing 35% growth rate increase time. Of 17 different medical departments sought PGx tests, Oncology department accounted for highest number, representing 58.47% all genotyped patients. total 1,000 were requested individuals susceptible receive dose modification genotype, 76 received genotype-guided adjustment. This study presents comprehensive descriptive real-world obtained public tertiary hospital specialized testing, strongly endorse integration into everyday practice.

Language: Английский

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