107,312 results match your criteria pharmacokinetic samples


Therapeutic review of cabotegravir/rilpivirine long-acting antiretroviral injectable and implementation considerations at an HIV specialty clinic.

Pharmacotherapy 2021 Jun 15. Epub 2021 Jun 15.

Indiana University Health, Indianapolis, Indiana, USA.

Cabotegravir/rilpivirine (CAB/RPV) was recently approved by the US Food and Drug Administration (FDA) as the first complete parenteral antiretroviral (ART) regimen for treatment of people living with HIV (PLWH). As a monthly intramuscular (IM) injection, this therapy constitutes a major departure from the traditional paradigm of oral therapy requiring (at least) daily administration that has defined HIV treatment for decades. Composed of a second-generation integrase inhibitor (INSTI) and nonnucleoside reverse transcriptase inhibitor (NNRTI), CAB/RPV has achieved high rates of sustained virologic suppression with a favorable safety profile for treatment-experienced PLWH following oral lead-in (OLI) during several clinical trials. Read More

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Recent trends in bioresponsive linker technologies of Prodrug-Based Self-Assembling nanomaterials.

Biomaterials 2021 Jun 5;275:120955. Epub 2021 Jun 5.

Faculty of Pharmaceutical Sciences, University of British Columbia, 2405 Wesbrook Mall, Vancouver, British Columbia, V6T 1Z3, Canada. Electronic address:

Prodrugs are designed to improve pharmaceutical properties of potent compounds and represent a central approach in drug development. The success of the prodrug strategy relies on incorporation of a reversible linkage facilitating controlled release of the parent drug. While prodrug approaches enhance pharmacokinetic properties over their parent drug, they still face challenges in absorption, distribution, metabolism, elimination, and toxicity (ADMET). Read More

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Pharmacokinetic study of Ninjin'yoeito: Absorption and brain distribution of Ninjin'yoeito ingredients in mice.

J Ethnopharmacol 2021 Jun 12:114332. Epub 2021 Jun 12.

Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan; Preppers Co. Ltd., 1-23-17 Kitashinagawa, Shinagawa Ward, Tokyo, 140-0001, Japan; International Mass Imaging Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan; Department of Systems Molecular Anatomy, Institute for Medical Photonics Research, Preeminent Medical Photonics Education & Research Center, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan. Electronic address:

Ethnopharmacological Relevance: Ninjin'yoeito (NYT), a Japanese traditional Kampo medicine, has been reported to exert various clinical benefits such as relief from fatigue, malaise, anorexia, frailty, sarcopenia, and cognitive dysfunction. Recently, some review articles described the pharmacological effects of NYT and additionally indicated the possibility that multiple ingredients in NYT contribute to these effects. However, pharmacokinetic data on the ingredients are essential in addition to data on their pharmacological activities to accurately determine the active ingredients in NYT. Read More

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Discovery and Optimization of a Novel 2-Pyrazolo[3,4-d]pyrimidine Derivative as a Potent Irreversible Pan-Fibroblast Growth Factor Receptor Inhibitor.

J Med Chem 2021 Jun 15. Epub 2021 Jun 15.

The State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, College of Pharmacy, Nankai University, Tianjin 300071, P. R. China.

Fibroblast growth factor receptors (FGFRs) have become promising therapeutic targets in various types of cancers. In fact, several selective irreversible inhibitors capable of covalently reacting with the conserved cysteine of FGFRs are currently being evaluated in clinical trials. In this article, we optimized and discovered a novel lead compound with remarkable inhibitory effects against FGFR (1-3), which is a derivative of 2-pyrazolo[3,4-d]pyrimidine. Read More

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Overall survival in metastatic melanoma correlates with pembrolizumab exposure and T cell exhaustion markers.

Pharmacol Res Perspect 2021 Aug;9(4):e00808

Calvary Mater Hospital Newcastle, Waratah, NSW, Australia.

Trial data support an absence of an exposure-survival relationship for pembrolizumab. As these relationships remain unexamined in a real-world setting, we determined them in metastatic melanoma prospectively in an observational study. Translational objectives included identifying biomarkers of progressive disease (PD). Read More

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Probenecid increases renal retention and antitumor activity of DFMO in neuroblastoma.

Cancer Chemother Pharmacol 2021 Jun 15. Epub 2021 Jun 15.

Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, 400 Monroe Ave, NW, Grand Rapids, MI, 49503, USA.

Background: Neuroblastoma (NB) is the most common extracranial solid tumor in children. Interference with the polyamine biosynthesis pathway by inhibition of MYCN-activated ornithine decarboxylase (ODC) is a validated approach. The ODC inhibitor α-difluoromethylornithine (DFMO, or Eflornithine) has been FDA-approved for the treatment of trypanosomiasis and hirsutism and has advanced to clinical cancer trials including NB as well as cancer-unrelated human diseases. Read More

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[Clinical applications of bevacizumab in the treatment of colorectal and ovarian cancer.]

Recenti Prog Med 2021 Jun;112(6):444-453

Ginecologia Oncologica, Fondazione Policlinico Universitario Gemelli IRCCS, Roma - Università Cattolica del Sacro Cuore, Roma.

The development of biological drugs, which began in the 1980s, has revolutionized the treatment of numerous oncological diseases and severely disabling autoimmune diseases, with widely demonstrated evidence of benefit. Today, biological drugs represent an important and continuously developing category and are used both as a support therapy in onco-hematology and as molecules with their own therapeutic activity, such as monoclonal antibodies. Among these, bevacizumab represents a drug of relevant clinical value, used as antiangiogenic therapy in numerous cancers, in particular colorectal and ovarian cancers. Read More

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Current opinion on the pharmacogenomics of paclitaxel-induced toxicity.

Expert Opin Drug Metab Toxicol 2021 Jun 15. Epub 2021 Jun 15.

Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.

: Paclitaxel is a microtubule stabilizer that is currently one of the most utilized chemotherapeutic agents. Its efficacy in breast, uterine, lung and other neoplasms made its safety profile enhancement a subject of great interest. Neurotoxicity is the most common paclitaxel-associated toxicities. Read More

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Pharmacokinetics, bioavailability and metabolism of neferine in rat by LC-MS/MS and LC-HRMS.

Biomed Chromatogr 2021 Jun 14:e5193. Epub 2021 Jun 14.

Department of Gerontology & Department of Surgery, Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science & Technology, Wuhan, China.

In this study, a simple and sensitive analytical method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated for the determination of neferine in rat plasma. After acetonitrile-mediated protein precipitation, the samples were separated on an ACQUITY BEH C column (2.1 × 50 mm, 1. Read More

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Preferential Oxycodone Loss of Physically Manipulated Abuse Deterrent Oxycodone HCl Extended Release Tablets Prepared for Nasal Insufflation Studies.

Pharm Res 2021 Jun 14. Epub 2021 Jun 14.

Department of Industrial and Physical Pharmacy, Purdue University, RHPH Building, RM 124, 575 Stadium Mall Dr, West Lafayette, Indiana, 47907, USA.

A method to reproducibly mill abuse deterrent oxycodone hydrochloride (HCl) extended release (ER) tablets was developed for a nasal insufflation pharmacokinetic (PK) study. Several comminution methods were explored before determining that a conical mill resulted in controlled milling of tablets to a size range equal to or below 1000 μm. However, milling resulted in significant loss of oxycodone from abuse deterrent oxycodone HCl ER tablets compared to minimal oxycodone loss from oxycodone HCl immediate release (IR) tablets. Read More

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Potential Natural Candidates in the Treatment of Coronavirus.

Authors:
Faisal Alsenani

Saudi J Biol Sci 2021 Jun 10. Epub 2021 Jun 10.

Department of Pharmacognosy, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia.

Many viral infections do not have treatments or resistant to existing antiviral therapeutic interventions, and a novel strategy is required to combat virus-mediated fatalities. A novel coronavirus (coronavirus disease 2019 [COVID-19]) emerged in Wuhan, China, in late 2019 and rapidly spread across the globe. COVID-19 has impacted human society with life-threatening and unprecedented health, social, and economic issues, and it continues to affect millions of people. Read More

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Metal-free carbon monoxide-releasing micelles undergo tandem photochemical reactions for cutaneous wound healing.

Chem Sci 2020 Apr 14;11(17):4499-4507. Epub 2020 Apr 14.

CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Science at the Microscale, Department of Polymer Science and Engineering, University of Science and Technology of China Hefei 230026 Anhui China

Carbon monoxide (CO) has shown broad biomedical applications. The site-specific delivery and controlled release of CO is of crucial importance to achieve maximum therapeutic benefits. The development of carbon monoxide (CO)-releasing polymers (CORPs) can increase the stability, optimize pharmacokinetic behavior, and reduce the side effects of small molecule precursors. Read More

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Targeted and modular architectural polymers employing bioorthogonal chemistry for quantitative therapeutic delivery.

Chem Sci 2020 Mar 6;11(12):3268-3280. Epub 2020 Mar 6.

Centre for Advanced Imaging, The University of Queensland Brisbane QLD 4072 Australia

There remain several key challenges to existing therapeutic systems for cancer therapy, such as quantitatively determining the true, tissue-specific drug release profile , as well as reducing side-effects for an increased standard of care. Hence, it is crucial to engineer new materials that allow for a better understanding of the pharmacokinetic/pharmacodynamic behaviours of therapeutics. We have expanded on recent "click-to-release" bioorthogonal pro-drug activation of antibody-drug conjugates (ADCs) to develop a modular and controlled theranostic system for quantitatively assessing site-specific drug activation and deposition from a nanocarrier molecule, by employing defined chemistries. Read More

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Tacrolimus Therapy in Adult Heart Transplant Recipients: Evaluation of a Bayesian Forecasting Software.

Ther Drug Monit 2021 Jun 8. Epub 2021 Jun 8.

St. Vincent's Clinical School, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia. Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Sydney, NSW, Australia. Ministry of Health, Putrajaya, Malaysia. School of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia. Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Sydney, NSW, Australia. Department of Pharmacy, St. Vincent's Hospital, Sydney, NSW, Australia. School of Medical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.

Background: Therapeutic drug monitoring is recommended to guide tacrolimus dosing because of its narrow therapeutic window and considerable pharmacokinetic variability. This study assessed tacrolimus dosing and monitoring practices in heart transplant recipients and evaluated the predictive performance of a Bayesian forecasting software using a renal transplant-derived tacrolimus model to predict tacrolimus concentrations.

Methods: A retrospective audit of heart transplant recipients (n=87) treated with tacrolimus was performed. Read More

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Preparation of Astaxanthin Micelles Self-Assembled by a Mechanochemical Method from Hydroxypropyl β-Cyclodextrin and Glyceryl Monostearate with Enhanced Antioxidant Activity.

Int J Pharm 2021 Jun 11:120799. Epub 2021 Jun 11.

National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, PR China; Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, PR China. Electronic address:

This research aimed to overcome the current challenges in the application of natural carotenoid antioxidants, such as their complex preparation processes, low bioavailability and poor drug stability. Herein, a mechanochemical method was used to prepare an inclusion complex (IC) that self-assembles into micelles in aqueous solution and achieves solid-phase loading of astaxanthin (AST). The NMR analysis, thermodynamics study, particle size analysis and electron microscopy image results showed that AST, hydroxypropyl β-cyclodextrin (HPβ-CD) and glyceryl monostearate (GMS) formed self-assembled micelles and maintained good stability in aqueous solution. Read More

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Generation of High-Quality Pharmacokinetic Data from Parallel Tail Vein Dosing and Bleeding in Non-cannulated Rats.

J Pharm Sci 2021 Jun 11. Epub 2021 Jun 11.

DMPK, Research and Early Development, Oncology R&D, AstraZeneca, Boston, US. Electronic address:

It is common practice to use cannulated rats for pharmacokinetic (PK) in-life studies as it yields high quality PK parameter estimation. While offering many benefits, cannulation requires surgery, post-surgical care, and cannula maintenance. As an alternative approach, the strategy of dosing and bleeding rats via the tail vein in a single experiment is technically feasible and theoretically offers many benefits. Read More

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Relationships between creatinine increase and mortality rates in patients given vancomycin in 76 hospitals: The increasing role of infectious disease pharmacists.

Am J Health Syst Pharm 2021 Jun 14. Epub 2021 Jun 14.

Becton, Dickinson and Company, Franklin Lakes, NJ, USA.

Purpose: Vancomycin is a commonly used antimicrobial with the potential for renal toxicity. We evaluated vancomycin duration, changes in renal function after vancomycin initiation ("post-vancomycin" renal function changes), and associated mortality risk among hospitalized patients.

Methods: We analyzed data from 76 hospitals and excluded patients with a baseline serum creatinine concentration (SCr) of >3. Read More

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Evaluating fostemsavir as a therapeutic option for patients with HIV.

Expert Opin Pharmacother 2021 Jun 14:1-7. Epub 2021 Jun 14.

Infectious Diseases Unit, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy.

ABSTRAC: Despite the unquestionable success of antiretroviral therapy achieved in recent years, there are still cases of heavily treated patients who do not achieve or struggle to maintain undetectable HIV-RNA due to drug resistance. New antiretroviral options are needed to address this issue.: The authors first provide an overview of fostemsavir and its role in the treatment of HTE PLWH. Read More

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Exposures of Phenylacetic Acid and Phenylacetylglutamine Across Different Subpopulations and Correlation with Adverse Events.

Clin Pharmacokinet 2021 Jun 14. Epub 2021 Jun 14.

Clinical Development, Mallinckrodt Pharmaceuticals, Hampton, NJ, 08827, USA.

Background: Elevated plasma ammonia is central to the pathogenesis of hepatic encephalopathy. Sodium phenylacetate or glycerol phenylbutyrate is approved for urea cycle disorders, but limited clinical data are available for hepatic encephalopathy. Phenylacetic acid (PAA) plasma exposure has been reported to correlate with neurologic adverse events in patients with cancer but not in patients with urea cycle disorders or hepatic encephalopathy. Read More

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Influence of CYP2D6 Phenotypes on the Pharmacokinetics of Aripiprazole and Dehydro-Aripiprazole Using a Physiologically Based Pharmacokinetic Approach.

Clin Pharmacokinet 2021 Jun 14. Epub 2021 Jun 14.

Department of Clinical Pharmacy, Institute of Pharmaceutical and Medical Chemistry, University of Münster, Corrensstr. 48, 48149, Münster, Germany.

Background And Objectives: Aripiprazole is an atypical antipsychotic drug that is metabolized by cytochrome P450 (CYP) 2D6 and CYP3A4, which mainly form its active metabolite dehydro-aripiprazole. Because of the genetic polymorphism of CYP2D6, plasma concentrations are highly variable between different phenotypes. In this study, phenotype-related physiologically based pharmacokinetic models were developed and evaluated to suggest phenotype-guided dose adjustments. Read More

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Antimicrobial Dose Reduction in Continuous Renal Replacement Therapy: Myth or Real Need? A Practical Approach for Guiding Dose Optimization of Novel Antibiotics.

Clin Pharmacokinet 2021 Jun 14. Epub 2021 Jun 14.

Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Via Massarenti, 9, 40138, Bologna, Italy.

Acute kidney injury represents a common complication in critically ill patients affected by septic shock and in many cases continuous renal replacement therapy (CRRT) may be required. In this scenario, antimicrobial dose optimization is highly challenging as the extracorporeal circuit may cause several pharmacokinetic alterations, which add up to volume of distribution and clearance variations resulting from sepsis. Variations in CRRT settings (i. Read More

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Sternal Intraosseous Devices: Review of the Literature.

West J Emerg Med 2021 Mar 24;22(3):690-695. Epub 2021 Mar 24.

Medical Command, Texas Army National Guard, Austin, Texas.

Introduction: The intraosseous (IO) route is one of the primary means of vascular access in critically ill and injured patients. The most common sites used are the proximal humerus, proximal tibia, and sternum. Sternal IO placement remains an often-overlooked option in emergency and prehospital medicine. Read More

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Skin Pharmacokinetics of Transdermal Scopolamine: Measurements and Modeling.

Mol Pharm 2021 Jun 14. Epub 2021 Jun 14.

Department of Pharmacy & Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, U.K.

Prediction of skin absorption and local bioavailability from topical formulations remains a difficult task. An important challenge in forecasting topical bioavailability is the limited information available about local and systemic drug concentrations post application of topical drug products. Commercially available transdermal patches, such as Scopoderm (Novartis Consumer Health UK), offer an opportunity to test these experimental approaches as systemic pharmacokinetic data are available with which to validate a predictive model. Read More

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Novel Antiplasmodial Compounds Leveraged with Multistage Potency against the Parasite : and Evaluations and Pharmacokinetic Studies.

J Med Chem 2021 Jun 14. Epub 2021 Jun 14.

Laboratory for Translational Chemistry and Drug Discovery, Department of Chemistry, Hansraj College University Enclave, University of Delhi, Delhi 110007, India.

Hydroxyethylamine (HEA)-based novel compounds were synthesized and their activity against 3D7 was assessed, identifying a few hits without any apparent toxicity. Hits and also exhibited activity against resistant field strains, RKL-9 and C580Y. A single dose, 50 mg/Kg, of hits administered to the rodent parasite ANKA exhibited up to 70% reduction in the parasite load. Read More

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Effect of Concomitant Hydroxyurea Therapy with Rutin and Gallic Acid: Integration of Pharmacokinetic and Pharmacodynamic Approaches.

ACS Omega 2021 Jun 25;6(22):14542-14550. Epub 2021 May 25.

PK-PD, Toxicology and Formulation Division, CSIR-Indian Institute of Integrative Medicine, Jammu, Jammu and Kashmir 180001, India.

Hydroxyurea (HU) is the first-ever approved drug by USFDA for sickle cell anemia (SCA). However, its treatment is associated with severe side effects like myelosuppression. Current studies are focused on the supplementation therapy for symptomatic management of SCA. Read More

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A Chemically Defined, Xeno- and Blood-Free Culture Medium Sustains Increased Production of Small Extracellular Vesicles From Mesenchymal Stem Cells.

Front Bioeng Biotechnol 2021 26;9:619930. Epub 2021 May 26.

Cells for Cells, Santiago, Chile.

Cell therapy is witnessing a notable shift toward cell-free treatments based on paracrine factors, in particular, towards small extracellular vesicles (sEV), that mimic the functional effect of the parental cells. While numerous sEV-based applications are currently in advanced preclinical stages, their promised translation depends on overcoming the manufacturing hurdles posed by the large-scale production of purified sEV. Unquestionably, the culture medium used with the parental cells plays a key role in the sEV's secretion rate and content. Read More

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Advances in Therapeutic Drug Monitoring in Biologic Therapies for Pediatric Inflammatory Bowel Disease.

Front Pediatr 2021 26;9:661536. Epub 2021 May 26.

Division of Pediatric Gastroenterology, Hepatology, and Nutrition, London Health Sciences Centre, Children's Hospital Western Ontario, Western University, London, ON, Canada.

In the current era of treat-to-target strategies, therapeutic drug monitoring (TDM) has emerged as a potential tool in optimizing the efficacy of biologics for children diagnosed with inflammatory bowel disease (IBD). The incorporation of TDM into treatment algorithms, however, has proven to be complex. "Proactive" TDM is emerging as a therapeutic strategy due to a recently published pediatric RCT showing a clear benefit of "proactive" TDM in anti-TNF therapy. Read More

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Using Liposomes to Alleviate the Toxicity of Chelerythrine, a Natural PKC Inhibitor, in Treating Non-Small Cell Lung Cancer.

Front Oncol 2021 27;11:658543. Epub 2021 May 27.

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Aim Of The Study: CHE can inhibit the proliferation of lung cancer cells and induce apoptosis. However, despite having toxicity, CHE has not been thoroughly investigated in term of its antitumor effect. The present study evaluated the antitumor effect of CHE on non-small cell lung cancer cell line HCC827. Read More

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Direct Oral Anticoagulants: From Randomized Clinical Trials to Real-World Clinical Practice.

Front Pharmacol 2021 26;12:684638. Epub 2021 May 26.

Science of Health Department, School of Medicine, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.

Direct oral anticoagulants (DOACs) are a more manageable alternative than vitamin K antagonists (VKAs) to prevent stroke in patients with nonvalvular atrial fibrillation and to prevent and treat venous thromboembolism. Despite their widespread use in clinical practice, there are still some unresolved issues on optimizing their use in particular clinical settings. Herein, we reviewed the current clinical evidence on uses of DOACs from pharmacology and clinical indications to safety and practical issues such as drugs and food interactions. Read More

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Population Pharmacokinetics of Ropeginterferon Alfa-2b: A Comparison Between Healthy Caucasian and Chinese Subjects.

Front Pharmacol 2021 28;12:673492. Epub 2021 May 28.

Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

To develop a population pharmacokinetic (PK) model for ropeginterferon alfa-2b and to compare its PK properties between Caucasian and Chinese populations. A population PK model was developed based on data from two phase I clinical trials conducted in Caucasian and Chinese individuals, to evaluate the influence of ethnicity on the PKs of ropeginterferon alfa-2b. We included 456 observations from 30 healthy Caucasian subjects and 438 observations from 27 healthy Chinese subjects in the population PK analysis. Read More

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