PubMed Journal Database | Clinical pharmacology and therapeutics RSS

09:06 EDT 27th May 2019 | BioPortfolio

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For example view all recent relevant publications on Epigenetics and associated publications and clincial trials.

Showing PubMed Articles 1–25 of 347 from Clinical pharmacology and therapeutics

Response to "Have We Found the Key to Unravel Treatment Development Lags for Rare Cancers?: MASTER KEY Project".

Have We Found the Key to Unravel Treatment Development Lags for Rare Cancers?: MASTER KEY Project.

An Old Drug for a New Indication: Repurposing Fenfluramine From an Anorexigen to an Antiepileptic Drug.

Information Patients Can Provide Will Strengthen the Real-World Evidence That Matters to Them.

Small But Mighty: The Use of Real-World Evidence to Inform Precision Medicine.

Capturing the complex interplay between drugs and the intestinal microbiome.

Predicting drug interactions, disposition, and side effects is central to the practice of clinical pharmacology. Until recently, the human microbiome has been an underappreciated player in the dynamics of drug metabolism. It is now clear that humans are 'superorganisms' with about tenfold more microbial cells than human cells and harboring an immense diversity of microbial enzymes. Owing to the advent of new technologies, we are beginning to understand the human microbiome's impact on clinical pharmacology....

PET Imaging of CRosuvastatin Hepatic Concentrations and Hepatobiliary Transport in Humans in the Absence and Presence of Cyclosporine A.

Using positron emission tomography (PET) imaging, we determined the hepatic concentrations and hepatobiliary transport of [ C]rosuvastatin (IV injection) in the absence (n=6) and presence (n=4 of 6) of cyclosporine A (CsA, IV infusion) following a therapeutic dose of unlabeled rosuvastatin (RSV) (5 mg, PO) in healthy human volunteers. The sinusoidal uptake, sinusoidal efflux and biliary efflux clearance (mL/min) of [ C]rosuvastatin, estimated through compartment modeling were 1205.6±384.8, 16.2±11.2 and 5...

Modulation of CYP450 activities in patients with type 2 diabetes.

We conducted a comprehensive in vivo study evaluating the influence of type 2 diabetes (T2D) on major CYP450 activities. These activities were assessed in 38 T2D and 35 non-T2D subjects after a single oral administration of a cocktail of probe drugs: 100mg caffeine (CYP1A2), 100mg bupropion (CYP2B6), 250mg tolbutamide (CYP2C9), 20mg omeprazole (CYP2C19), 30mg dextromethorphan (CYP2D6), 2mg midazolam (CYP3As), and 250mg chlorzoxazone (alone) (CYP2E1). Mean metabolic activity for CYP2C19, CYP2B6 and CYP3A wer...

Nivolumab Clearance Is Stationary in Resected Melanoma Patients on Adjuvant Therapy: Implications of Disease Status on Time-Varying Clearance.

Nivolumab clearance (CL) in patients with advanced melanoma (MEL) decreases over the treatment duration with change in CL associated with improved disease status, measured by reduced tumor burden. Here, we characterize the pharmacokinetics of nivolumab administered as adjuvant therapy for patients with melanoma whose tumors were removed by surgical resection (AdjMEL). A population pharmacokinetic model was developed using data from 1773 patients with AdjMEL, MEL, non-small cell lung cancer, and other solid ...

The US Food and Drug Administration's Model-Informed Drug Development Paired Meeting Pilot Program: Early Experience and Impact.

Catechol O-Methyltransferase Pharmacogenomics: Challenges and Opportunities.

Pharmacokinetic/ Pharmacodynamic Modeling To Support The Re-Approval Of Gemtuzumab Ozogamicin.

Gemtuzumab ozogamicin (Mylotarg ) was the first antibody-drug conjugate to be approved - for CD33-positive acute myeloid leukemia (AML). However, it was voluntarily withdrawn from the US market due to lack of clinical benefit in the confirmatory Phase 3 trial. In 2012, several investigator cooperative studies using a different dosing regimen showed efficacy, but pharmacokinetic data were not collected in these trials. Through simulation of expected concentrations for new dosing regimens, pharmacokinetic/ ph...

Development of the PGx-Passport: A Panel of Actionable Germline Genetic Variants for Pre-emptive Pharmacogenetic Testing.

Pre-emptive pharmacogenetic (PGx) testing of a panel of germline genetic variants represents a new model for personalised medicine. Clinical impact of PGx testing is maximized when all variant alleles for which actionable clinical guidelines are available, are included in the test panel. However, no such standardized method has been presented to date, impeding adoption, exchange and continuity of PGx testing. We, therefore, developed such a panel, hereafter called the PGx-Passport, based on the actionable D...

Using healthcare databases to refine understanding of exploratory associations between drugs and progression of open angle glaucoma.

We sought to refine understanding about associations identified in prior studies between angiotensin-II receptor blockers, metformin, selective serotonin reuptake inhibitors, fibric-acid derivatives, or calcium channel blockers and progression to glaucoma filtration surgery for open angle glaucoma (OAG). We used new-initiator, active-comparator cohort designs to investigate these drugs in two data sources. We adjusted for confounders using stabilized inverse-probability-of-treatment weights and evaluated re...

The advantages and challenges of diversity in Pharmacogenomics: Can minority populations bring us closer to implementation?

Health disparities exist among minorities in the United States, with differences seen in disease prevalence, mortality, and responses to medications. These differences are multifactorial with genetic variation explains a portion of this variability. Pharmacogenomics aims to find the effect of genetic variations on drug response, with the goal of optimizing drug therapy and development. Although genome-wide association studies have been useful in unbiasedly surveying the genome for genetic drivers of clinica...

Decentralized Trials in the Age of Real-World Evidence and Inclusivity in Clinical Investigations.

Can Digital Health Enable Higher Quality Real-World Evidence-Based Decisions?

Predictive analysis of first Abbreviated New Drug Application submission for new chemical entities based on machine learning methodology.

Generic drug products are approved by the US Food and Drug Administration (FDA) through Abbreviated New Drug Applications (ANDA). The ANDA review and approval involves multiple offices across the FDA. Forecasting ANDA submissions can critically inform resource allocation and workload management. In this work, we employed machine learning methodologies to predict the time to first ANDA submissions referencing new chemical entities (NCE) following their earliest lawful ANDA submission dates. Drug product info...

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2B6 and Efavirenz-containing Antiretroviral Therapy.

The human immunodeficiency virus (HIV) type-1 non-nucleoside reverse transcriptase inhibitor, efavirenz, is widely used to treat HIV-1 infection. Efavirenz is predominantly metabolized into inactive metabolites by CYP2B6, and patients with certain CYP2B6 genetic variants may be at increased risk for adverse effects, particularly central nervous system toxicity and treatment discontinuation. We summarize the evidence from the literature and provide therapeutic recommendations for efavirenz prescribing based ...

Navigating the Labyrinth of Pharmacogenetic Testing: A Guide to Test Selection.

Come Dance With Me: Transformative Changes in the Science and Practice of Drug-Drug Interactions.

The past 2 decades have witnessed transformative changes in our approach to drug-drug interactions (DDIs) from scientific research to clinical practice. Collaborative cooperation across the sectors of academia, pharmaceutical industry, providers of translational research tools and services, global regulatory agencies, and healthcare providers has created and galvanized a science-informed and patient-centered approach. Multidisciplinary innovations in mechanistic assessment of absorption, distribution, meta...

A Realistic Review of the Drug-Injury Relief System in Taiwan: Challenges, Lessons, and Achievements.

The drug injury relief system in Taiwan was implemented 20 years ago, with the goal of providing timely relief for drug injuries incurred by the proper use of legal drugs. This system utilizes a non-litigation expert review process to evaluate drug injury relief applications, and 2,732 applications have been reviewed from 1999 to 2016. Of these, 1,572 applications received relief payments, an approval rate of 58%. Average review timeframes per application have decreased from 248 days (2003-2011) to 182 days...

An Overview of Genomic Biomarker Use in Cardiovascular Disease Clinical Trials.

Clinical trial designs targeting patient subgroups with certain genetic characteristics may enhance the efficiency of developing drugs for cardiovascular disease (CVD). To evaluate the extent to which genetic knowledge translates to the CVD pipeline, we analyzed how genomic biomarkers are utilized in trials. Phase 2 and 3 trial protocols for investigational new drugs for CVD and risk factors were evaluated for prospective and exploratory genomic biomarker use; drug targets were evaluated for the presence of...

Use of 4β-hydroxycholesterol plasma concentrations as an endogenous biomarker of CYP3A activity: Clinical validation in individuals with type 2 diabetes.

The relevance of endogenous 4β-hydroxycholesterol (4β-OHC) plasma concentrations or of the 4β-OHC/total cholesterol concentration ratio (4β-OHC ratio) as surrogate markers of CYP3A activity was evaluated in individuals with (n=38) or without (n=35) type 2 diabetes (T2D). Midazolam was used as a comparator to validate exploratory measures of phenotypic CYP3A activity. Metabolic ratios (MR) of orally administered midazolam in the non-diabetic and diabetic populations correlated significantly with 4β-OHC ...

Population modeling highlights drug disposition differences between tenofovir alafenamide and tenofovir disoproxil fumarate in the blood and semen.

Understanding antiretroviral disposition in the male genital tract, a distinct viral compartment, can provide insight for HIV eradication. Population pharmacokinetic modeling was conducted to investigate the disposition of tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and emtricitabine and their metabolites in blood and semen. Blood plasma and seminal plasma (SP) concentrations of tenofovir and emtricitabine, and tenofovir-diphosphate and emtricitabine-triphosphate concentrations in the ...

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