Drugs in R&D

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

List of Papers (Total 317)

A Phase I Study of the Pharmacokinetics and Pharmacodynamics of Intranasal Doxylamine in Subjects with Chronic Intermittent Sleep Impairment

IntroductionDoxylamine tablets are approved as an over-the-counter sleep aid. We developed a doxylamine succinate intranasal metered-dose delivery system with the expectation of a more rapid onset of action with reduced side-effect potential compared with the oral tablet.MethodsThis phase I study randomized 24 adults with chronic intermittent sleep impairment to receive either...

The Many Faces of Apomorphine: Lessons from the Past and Challenges for the Future

Apomorphine is now recognized as the oldest antiparkinsonian drug on the market. Though still underused, it is increasingly prescribed in Europe for patients with advanced Parkinson’s disease (PD) with motor fluctuations. However, its history is far from being limited to movement disorders. This paper traces the history of apomorphine, from its earliest empirical use, to its...

Second-Hand Exposure of Staff Administering Vaporised Cannabinoid Products to Patients in a Hospital Setting

Background In many health settings, administration of medicinal cannabis poses significant implementation barriers including drug storage and safety for administering staff and surrounding patients. Different modes of administration also provide different yet potentially significant issues. One route that has become of clinical interest owing to the rapid onset of action and...

Effects of a Fixed-Dose Co-Formulation of Daclatasvir, Asunaprevir, and Beclabuvir on the Pharmacokinetics of a Cocktail of Cytochrome P450 and Drug Transporter Substrates in Healthy Subjects

Background A fixed-dose combination of daclatasvir (DCV; hepatitis C virus NS5A inhibitor), asunaprevir (ASV; non-structural protein 3 inhibitor), and beclabuvir (BCV; non-structural protein 5B inhibitor) is approved in Japan for hepatitis C virus genotype 1. Objective The objective of this study was to assess the combination’s drug–drug interaction potential in vivo using a...

The Risk of Thrombocytopenia During Valproic Acid Therapy: A Critical Summary of Available Clinical Data

Valproate is an effective anti-epileptic and mood stabilizer drug, but its prescription may be complicated by the development of thrombocytopenia. The purpose of the present manuscript is to provide a critical overview about the risk of thrombocytopenia during treatment with valproate. A search of the main database sources has been conducted to identify relevant papers about the...

Sealing Effects on the Storage Stability of the Cyanide Antidotal Candidate, Dimethyl Trisulfide

Background Dimethyl trisulfide (DMTS) is a highly lipid-soluble cyanide (CN) antidote candidate molecule. In prior studies with various US FDA-approved co-solvents, surfactants, and their combinations, aqueous solutions containing 15% polysorbate 80 (Poly80) were found to effectively solubilize DMTS in formulations for intramuscular administration. However, DMTS formulated in 15...

Efficacy and Safety of Nintedanib for the Treatment of Idiopathic Pulmonary Fibrosis: An Update

Idiopathic pulmonary fibrosis is a fatal form of progressive fibrosing interstitial pneumonia with limited treatment options. In recent years, its management has been transformed with the approval of two new antifibrotic drugs: nintedanib and pirfenidone. Nintedanib is a tyrosine kinase inhibitor that efficiently slows idiopathic pulmonary fibrosis progression and has an...

Intranasal Therapy to Stop Status Epilepticus in Prehospital Settings

Status epilepticus (SE) is a medical emergency characterized by uncontrolled, prolonged seizures with rapid and widespread neuronal damage. Patients that suffer from longer episodes of SE are more likely to have poorer clinical outcomes and a higher cost of healthcare. Understanding novel molecular mechanisms that regulate inhibitory and excitatory neurotransmission that initiate...

Bioavailability of Orally Administered Des-Aspartate-Angiotensin I in Human Subjects

In an earlier single-dose escalation study to evaluate the safety and pharmacokinetics of orally administered des-aspartate-angiotensin I (DAA-I) in healthy subjects, the plasma level of DAA-I could not be determined because DAA-I is rapidly degraded in the circulation. The present study investigated the oral bioavailability of DAA-I by measuring the prostaglandin E2 metabolite...

A Randomized Multiple Dose Pharmacokinetic Study of a Novel PDE10A Inhibitor TAK-063 in Subjects with Stable Schizophrenia and Japanese Subjects and Modeling of Exposure Relationships to Adverse Events

Background Phosphodiesterase 10A (PDE10A) is selectively expressed in medium spiny neurons of the striatum. TAK-063 is a selective inhibitor of PDE10A in clinical development for the treatment of schizophrenia. Objectives Safety, tolerability, and pharmacokinetics (PK) of TAK-063 were evaluated following multiple rising oral doses, and PK/adverse event (AE) models were developed...

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...

Serious Adverse Events Among SPRINT Trial Participants Taking Statins at Baseline

Background Real-world evidence of statin side effects is potentially biased because statin use is neither randomized nor unblinded. An innovative study design can mitigate these biases. For example, in the recent ASCOT-LLA trial, patient-reported adverse events such as muscle pain and weakness were higher in the non-randomized and non-blinded setting than in the randomized...

Switching Between Biological Treatments in Psoriatic Arthritis: A Review of the Evidence

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy. Therapy with anti-tumor necrosis factor (TNF)-α agents represents the first therapeutic choice for moderate and severe forms; however, PsA patients can experience anti-TNFα failure, lack of efficacy, or adverse events. Several evidences exist on the effectiveness of switching among different TNFα inhibitors, and we...

Transmucosal Delivery of Nicotine in Combination with Tincture of Benzoin Inhibits Apoptosis

Background and Objective The aim of this study was to test the hypothesis that tincture of benzoin (TOB) facilitates immediate transmucosal nicotine absorption while simultaneously promoting a safe and sustained delivery of the nicotine. Methods In combination with TOB, nicotine toxicity and diffusion across human mucosal cells were measured using a 3-D human mucosal tissue model...

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...

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...

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...