Drugs in R&D

http://link.springer.com/journal/40268

List of Papers (Total 298)

The Adherence Rate Threshold is Drug Specific

Introduction Patient adherence to a medication regimen is usually expressed as an adherence rate, defined as the proportion of prescribed doses actually taken. An adherence rate threshold, above which the therapeutic effect is maintained, is typically assigned an arbitrary value, commonly 0.8. Objective Here, we determined the value of the adherence rate threshold objectively in ...

Identification of Polymorphic Forms of Active Pharmaceutical Ingredient in Low-Concentration Dry Powder Formulations by Synchrotron X-Ray Powder Diffraction

Background The identification of different (pseudo) polymorphs of an active pharmaceutical ingredient in dry powder formulations is of importance during development and entire product lifecycle, e.g., quality control. Whereas determination of polymorphic differences of pure substances is rather easy, in dry powder formulations, it is generally difficult and the difficulties ...

Pharmacokinetics of a New Oral Vitamin D Receptor Activator (2-Methylene-19-Nor-(20S)-1α,25-Dihydroxyvitamin D3) in Patients with Chronic Kidney Disease and Secondary Hyperparathyroidism on Hemodialysis

Background 2-Methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D3 (DP001 or 2MD) is a novel, potent 1α-hydroxylated vitamin D analog that binds to the vitamin D receptor and suppresses parathyroid hormone synthesis and secretion with potential for an improved safety profile compared to existing active vitamin D analogs. The purpose of this study was to evaluate the pharmacokinetics of ...

Feasibility, Safety, and Efficacy of an Alternative Schedule of Sunitinib for the Treatment of Patients with Metastatic Renal Cell Carcinoma: A Retrospective Study

Background Standard treatment with sunitinib for patients with metastatic renal cancer provides an ‘on-off’ schedule (daily administration of a 50-mg capsule for 4 weeks, followed by a 2-week break; consecutive 6-week cycles). We developed an alternative intermittent schedule to reduce the toxicity and symptoms of tumor regrowth during the rest period and to allow prolonged ...

Impact of Etoposide on BRCA1 Expression in Various Breast Cancer Cell Lines

Breast cancer 1 (BRCA1), as a tumor suppressor, exerts an effective influence on protecting DNA integrity to suppress the development of breast cancer (BC). BRCA1 expression is induced in response to DNA-damaging agents such as etoposide. Germline BRCA1 gene mutations are associated with development of hereditary BC. However, besides BRCA-mutated BCs, some sporadic cancers may also ...

Pharmacokinetic Effects of Antidrug Antibodies Occurring in Healthy Subjects After a Single Dose of Intravenous Infliximab

Background Infliximab pharmacokinetic studies have been performed in patients receiving chronic infliximab therapy. In these patients, infliximab antidrug antibodies (ADAs) increase infliximab clearance and decrease serum levels and drug efficacy. Objective This study analyzed the pharmacokinetic effect of infliximab ADAs in healthy subjects receiving a single dose of intravenous ...

Adverse Event Profile of Pyrimethamine-Based Therapy in Toxoplasmosis: A Systematic Review

Introduction Approximately a third of the population worldwide is chronically infected with Toxoplasma gondii. Pyrimethamine-based regimens are recommended for the treatment of toxoplasmosis. Objective The aim was to evaluate the safety profile of pyrimethamine-based treatment for the three main Toxoplasma manifestations: toxoplasmic encephalitis (TE), ocular toxoplasmosis, and ...

Boceprevir and Antiretroviral Pharmacokinetic Interactions in HIV/HCV Co-infected Persons: AIDS Clinical Trials Group Study A5309s

Objective The objective of this study was to determine the magnitude of drug interactions between the hepatitis C virus (HCV) protease inhibitor boceprevir (BOC) and antiretroviral (ARV) agents in persons with HIV/HCV co-infection. Methods Participants taking two nucleos(t)ide analogs with either efavirenz, raltegravir, or ritonavir-boosted atazanavir, darunavir, or lopinavir ...

Benzodiazepines and Z-Drugs: An Updated Review of Major Adverse Outcomes Reported on in Epidemiologic Research

Various adverse events resulting from, or associated with, benzodiazepine and/or Z-drug use have been extensively reported on and discussed in great detail within the biomedical literature. It is widely accepted that motor vehicle accidents and falls leading to fractures in older adults are major adverse events that have been shown to occur more frequently in users of ...

Longitudinal Assessment of the Effect of Atrasentan on Thoracic Bioimpedance in Diabetic Nephropathy: A Randomized, Double-Blind, Placebo-Controlled Trial

Background Fluid retention is a common adverse event in patients who receive endothelin (ET) receptor antagonist therapy, including the highly selective ETA receptor antagonist, atrasentan. Objective We performed longitudinal assessments of thoracic bioimpedance in patients with type 2 diabetes mellitus and nephropathy to determine whether a decrease in bioimpedance accurately ...

The EGFR Inhibitor Gefitinib Enhanced the Response of Human Oral Squamous Cell Carcinoma to Cisplatin In Vitro

Introduction The epidermal growth factor receptor (EGFR) is highly expressed in a variety of solid tumors including oral cavity squamous cell carcinoma (OSCC) and has been implicated in the resistance of these tumors to cisplatin. This study was performed to determine if the EGFR tyrosine kinase inhibitor gefitinib could enhance the cytotoxic effect of cisplatin on OSCC cells in ...

Methodological Study of Vancomycin Dosing in Elderly Patients Using Actual Serum Creatinine Versus Rounded Serum Creatinine

Purpose The practice of intentional rounding up of serum creatinine (SCr) in elderly patients with low measured values can lead to an underestimation of creatinine clearance and subsequent inaccurate dosing of medications. Thus, the purpose of this study was to evaluate the accuracy of vancomycin dose calculations for patients aged ≥65 years using an SCr rounded up to 1 mg/dL ...

Does Dose Modification Affect Efficacy of First-Line Pazopanib in Metastatic Renal Cell Carcinoma?

Background Pazopanib is a standard treatment for metastatic renal cell carcinoma (mRCC), and 800 mg/daily is considered the optimal dose. However, some patients require dose modification because of toxicity. Whether a reduced dose of pazopanib is as effective as the standard dose in achieving clinical benefit remains unclear. Objectives Our objective was to conduct a retrospective ...

Differences in Dihydrotetrabenazine Isomer Concentrations Following Administration of Tetrabenazine and Valbenazine

Background Tetrabenazine (TBZ) activity is thought to result from four isomeric dihydrotetrabenazine (HTBZ) metabolites ([+]-α-HTBZ, [−]-α-HTBZ, [+]-β-HTBZ, [−]-β-HTBZ). Each isomer has a unique profile of vesicular monoamine transporter 2 (VMAT2) inhibition and off-target binding. Previously published data only report total isomer (α) and (β) concentrations. We developed a method ...

A Randomized, Open-Label, Two-Way Crossover, Single-Dose Bioequivalence Study of Temozolomide 200 mg/m2 (Dralitem® vs. Temodal® Capsules) in Patients with Primary Tumors of the Central Nervous System Under Fasting Conditions

Background Temozolomide is an antineoplastic agent of proven efficacy against high-grade gliomas. Purpose The objective of this crossover, single-dose, bioequivalence study was to compare the rate and extent of absorption of oral temozolomide after administration of the study product (Dralitem®, Monte Verde Sociedad Anónima) and the reference product (Temodal®, originator product ...

Impact of Genetic Polymorphisms on Phenytoin Pharmacokinetics and Clinical Outcomes in the Middle East and North Africa Region

Background Genetic polymorphisms are known to influence outcomes with phenytoin yet effects in the Middle East and North Africa region are poorly understood. Objectives The objective of this systematic review was to evaluate the impact of genetic polymorphisms on phenytoin pharmacokinetics and clinical outcomes in populations originating from the Middle East and North Africa ...

Breakthrough Pain Management with Sublingual Fentanyl Tablets in Patients with Cancer: Age Subgroup Analysis of a Multicenter Prospective Study

Introduction Breakthrough pain (BTP) management in patients with cancer is challenging, especially in the elderly. However, no studies examining the influence of age on BTP medication have been conducted. The aim of this work was to investigate the effect of sublingual fentanyl tablets (SFTs) in terms of efficacy, safety, and quality of life in two age categories. Methods We ...

Eslicarbazepine Acetate: A New Improvement on a Classic Drug Family for the Treatment of Partial-Onset Seizures

Eslicarbazepine acetate is a new anti-epileptic drug belonging to the dibenzazepine carboxamide family that is currently approved as adjunctive therapy and monotherapy for partial-onset (focal) seizures. The drug enhances slow inactivation of voltage-gated sodium channels and subsequently reduces the activity of rapidly firing neurons. Eslicarbazepine acetate has few, but some, ...

Effectiveness and Safety of Switching from Innovator Infliximab to Biosimilar CT-P13 in Inflammatory Rheumatic Diseases: A Real-World Case Study

Objective CT-P13 is a biosimilar with comparable pharmacokinetics, efficacy and safety to its reference product (RP), infliximab. Studies have shown that switching from RP to CT-P13 does not reduce the effectiveness or safety of treatment. Methods In this retrospective real-world study, patients with inflammatory diseases treated with RP were switched to CT-P13 (n = 7) or continued ...

Lipophilicity Influences Drug Binding to α1-Acid Glycoprotein F1/S Variants But Not to the A Variant

Objective Human α1-acid glycoprotein has genetic variants, the F1, S, and A variants, which can be separated isoelectrophoretically. These variants show differences in their affinity of binding to several drugs. In this study, we investigated the factors determining drug binding to these α1-acid glycoprotein genetic variants using disopyramide, warfarin, and tamsulosin as marker ...

A Dipeptidyl Peptidase-4 Inhibitor, Teneligliptin, Decreases Plasma Triglyceride-Rich Lipoprotein Remnants in Diabetic Patients with Chronic Kidney Disease Undergoing Hemodialysis

Objective A high plasma level of remnant-like particle cholesterol (RLP-C), which is equivalent to triglyceride-rich lipoprotein remnant, is an important coronary risk marker. RLP-C level is high, independent of other plasma lipids, in patients with chronic kidney disease (CKD) undergoing hemodialysis. The effect of teneligliptin, a dipeptidyl peptidase (DPP)-4 inhibitor, on plasma ...

Comparative Effect of Calcium Channel Blockers on Glomerular Function in Hypertensive Patients with Diabetes Mellitus

Background We conducted a retrospective cohort study to evaluate and compare the longitudinal effect of monotherapy with L-, L/T-, L/N-, and L/N/T-type calcium channel blockers (CCBs) on estimated glomerular filtration rate (eGFR), and to investigate the association of treatment duration with eGFR in diabetic patients with hypertension. Methods Using a clinical database, we ...

Pharmacokinetics of Bevacizumab in Three Patients Under the Age of 3 Years with CNS Malignancies

Background Bevacizumab is a recombinant antibody that is increasingly used in pediatric malignancies. The pharmacokinetics of bevacizumab in pediatric patients have been shown to be influenced by tumor localization and body weight. In this report, we present data on the pharmacokinetics and safety of bevacizumab in children under the age of 3 years with central nervous system (CNS) ...

Comparison of Generic Drug Reviews for Marketing Authorization between Japan and Canada

Purpose Generic drugs are assuming an increasingly important role in sustaining modern healthcare systems, as the cost of healthcare, including drug usage, is gradually expanding around the world. To date, published articles comparing generic drug reviews between different countries are scarce. Objective The objective of this study was to examine generic drug reviews in Japan and ...

A Phase I Study of Combination Therapy with Sorafenib and 5-Fluorouracil in Patients with Advanced Hepatocellular Carcinoma

Background and aims Sorafenib is the first molecular targeted drug approved for the treatment of advanced hepatocellular carcinoma (HCC) and is a potent small molecule inhibitor of multiple kinases. Combination therapy with sorafenib and other cytotoxic agents for HCC may result in additive anticancer activity. The purpose of this phase I study was to investigate the safety and ...