Population Pharmacokinetic Model of Plasma and Cellular Mycophenolic Acid in Kidney Transplant Patients from the CIMTRE Study
ConclusionThis population pharmacokinetic model demonstrated the intracellular accumulation of MPA, the efflux of MPA out of the cells being dependent on P-glycoprotein transporters. Nevertheless, further studies are warranted to investigate the relevance of MPA concentrations in peripheral blood mononuclear cells to dosing regimen optimisation. (Source: Drugs in R&D)
Source: Drugs in R&D - October 5, 2020 Category: Drugs & Pharmacology Source Type: research
Systematic Review: Monoclonal Antibody-Induced Subacute Cutaneous Lupus Erythematosus
ConclusionWe present the first systematic review characterising mAb-induced SCLE with respect to triggers, clinical signs, laboratory findings, prognosis and treatment approaches. We identify elevated rates associated with the use of checkpoint inhibitors and anti-TNF ɑ agents. (Source: Drugs in R&D)
Source: Drugs in R&D - September 21, 2020 Category: Drugs & Pharmacology Source Type: research
Comparability Considerations and Challenges for Expedited Development Programs for Biological Products
This article highlights discussions from the workshop. (Source: Drugs in R&D)
Source: Drugs in R&D - September 9, 2020 Category: Drugs & Pharmacology Source Type: research
Nimodipine Pharmacokinetic Variability in Various Patient Populations
AbstractNimodipine has been shown to improve outcomes following aneurysmal subarachnoid hemorrhage. Guidelines recommend that all patients receive a fixed dose of oral nimodipine for 21 days. However, pharmacokinetic studies have suggested variability of nimodipine pharmacokinetics in subarachnoid hemorrhage and in other patient populations. The clinical relevance of such variability is unknown. Therefore, the objective of the present review is, first, to conduct a literature rev iew and summarize nimodipine pharmacokinetic data and sources of variability in various patient groups. Second, to determine if there is any ev...
Source: Drugs in R&D - September 8, 2020 Category: Drugs & Pharmacology Source Type: research
Remimazolam Has Low Oral Bioavailability and No Potential for Misuse in Drug-Facilitated Sexual Assaults, with or Without Alcohol: Results from Two Randomised Clinical Trials
ConclusionThe oral bioavailability of remimazolam is negligible, which —together with its distinct bitter taste—suggests no meaningful potential for misuse in drug-facilitated sexual assaults via oral ingestion, with or without alcohol.Clinical Trial Registration NumbersTrial 1 (NCT04113564) and trial 2 (NCT04113343) both retrospectively registered on 2 October 2019. (Source: Drugs in R&D)
Source: Drugs in R&D - August 12, 2020 Category: Drugs & Pharmacology Source Type: research
Combined Intravenous Sildenafil and l -Arginine Administration in a Porcine Animal Model: Hemodynamic Safety Profile and Effects on Coronary Blood Flow
ConclusionsThe combined intravenous administration of sildenafil andl-arginine in a porcine animal model was safe, well tolerated, and had at least additive effects on left anterior descending artery blood flow. Simultaneous application of both drugs might have dose-sparing effects leading to desired coronary effects at lower and safer sildenafil andl-arginine plasma concentrations. Hyperosmolality was only a minor factor inl-arginine hemodynamic effects. (Source: Drugs in R&D)
Source: Drugs in R&D - July 26, 2020 Category: Drugs & Pharmacology Source Type: research
Fingolimod as a Treatment in Neurologic Disorders Beyond Multiple Sclerosis
AbstractFingolimod is an approved treatment for relapsing –remitting multiple sclerosis (MS), and its properties in different pathways have raised interest in therapy research for other neurodegenerative diseases. Fingolimod is an agonist of sphingosine-1-phosphate (S1P) receptors. Its main pharmacologic effect is immunomodulation by lymphocyte homing, t hereby reducing the numbers of T and B cells in circulation. Because of the ubiquitous expression of S1P receptors, other effects have also been described. Here, we review preclinical experiments evaluating the effects of treatment with fingolimod in neurodegenerative di...
Source: Drugs in R&D - July 21, 2020 Category: Drugs & Pharmacology Source Type: research
Population Pharmacokinetics of Magnesium Sulfate in Preeclampsia and Associated Factors
ConclusionThe PK of MgSO4 in pregnant women with PE is significantly affected by creatinine and body weight. Pregnant women with PE and higher body weight have a higherV and, consequently, a lower elimination rate of MgSO4. Pregnant women with PE and a higher serum creatinine value show lower CL and, therefore, lower MgSO4 elimination rate. (Source: Drugs in R&D)
Source: Drugs in R&D - July 7, 2020 Category: Drugs & Pharmacology Source Type: research
Pexidartinib (TURALIO ™): The First FDA-Indicated Systemic Treatment for Tenosynovial Giant Cell Tumor
AbstractTenosynovial giant cell tumor is a rare proliferative tumor that arises from the synovium, bursae, or tendon sheaths due to an overproduction of colony-stimulating factor 1. Historically, treatment options for patients with local or diffuse tenosynovial giant cell tumor have been limited to surgical interventions. However, for some patients, surgical resection could worsen functional limitations and/or morbidity. In August 2019, the FDA approved pexidartinib (TURALIO ™, Daiichi Sankyo), the first systemic treatment option for adult patients with symptomatic tenosynovial giant cell tumor associated with severe mor...
Source: Drugs in R&D - July 1, 2020 Category: Drugs & Pharmacology Source Type: research
Identification of a Potential Peptide Inhibitor of SARS-CoV-2 Targeting its Entry into the Host Cells
ConclusionOur findings suggest that computationally developed inhibitory peptide may be developed as an anti-SARS-CoV-2 agent for the treatment of SARS-CoV-2 infection. We further plan to pursue the peptide in cell-based assays and eventually for clinical trials. (Source: Drugs in R&D)
Source: Drugs in R&D - June 25, 2020 Category: Drugs & Pharmacology Source Type: research
Ex-vivo Sensitivity of Plasmodium falciparum to Common Anti-malarial Drugs: The Case of K éniéroba, a Malaria Endemic Village in Mali
ConclusionsPlasmodium falciparum isolates were highly sensitive to dihydroartermisinin, lumefantrine, and piperaquine and less sensitive to amodiaquine (n = 2), mefloquine (n = 1), and quinine (n = 19). Therefore, our data support the previously reported increasing trend in chloroquine sensitivity in Mali. (Source: Drugs in R&D)
Source: Drugs in R&D - June 17, 2020 Category: Drugs & Pharmacology Source Type: research
Cutaneous Adverse Events in Newly Approved FDA Non-cancer Drugs: A Systematic Review
AbstractThe prevalence of cutaneous adverse events attributable to newly approved anti-cancer drugs has been well reviewed in the dermatologic literature. In contrast, over 75% of US Food and Drug Administration approvals in the past 5 years have been for non-cancer drugs and indications. This represents multiple other categories of approved medications associated with cutaneous adverse reactions. To investigate the cutaneous adverse events associated with these potentially neglected medications, a systematic review was conducte d. Two hundred and forty-one medications approved by the Food and Drug Administration between...
Source: Drugs in R&D - June 16, 2020 Category: Drugs & Pharmacology Source Type: research
Evaluation of Fixed-Dose Combinations of Ibuprofen and Acetaminophen in the Treatment of Postsurgical Dental Pain: A Pilot, Dose-Ranging, Randomized Study
ConclusionEach IBU/APAP FDC provided analgesic efficacy comparable to that with ibuprofen 400 mg and superior to that with placebo. Each FDC provided MPR in < 1 h, duration of pain relief > 9 h, and tolerability similar to that with ibuprofen and placebo.ClinicalTrials.gov RegistrationNCT01559259 (Source: Drugs in R&D)
Source: Drugs in R&D - June 5, 2020 Category: Drugs & Pharmacology Source Type: research
In-Vitro Sorbent-Mediated Removal of Edoxaban from Human Plasma and Albumin Solution
ConclusionSorbent-mediated technology may represent a viable pathway for edoxaban removal from human plasma or albumin solution. (Source: Drugs in R&D)
Source: Drugs in R&D - May 14, 2020 Category: Drugs & Pharmacology Source Type: research
Intravenous Tramadol is Effective in the Management of Postoperative Pain Following Abdominoplasty: A Three-Arm Randomized Placebo- and Active-Controlled Trial
ConclusionThe study demonstrated that IV tramadol 50 mg is highly effective in the management of postoperative pain following abdominoplasty. The consistency of effects between tramadol and morphine (as compared to placebo) for primary and key secondary endpoints validates the efficacy of tramadol observed. The study also provided direct evidence of improved tolerability of IV tramadol over a standard-of-care conventional Schedule II opioid. IV tramadol may become a useful option in patients where exposure to conventional opioids is not desired. (Source: Drugs in R&D)
Source: Drugs in R&D - May 13, 2020 Category: Drugs & Pharmacology Source Type: research
