Dataset Information

New and Old Horizons for an Ancient Drug: Pharmacokinetics, Pharmacodynamics, and Clinical Perspectives of Dimethyl Fumarate.

ABSTRACT: (1) Background: In their 60-year history, dimethyl fumarate and other salts of fumaric acid have been used for the treatment of psoriasis and other immune-mediated diseases for their immune-modulating properties. Over the years, new mechanisms of action have been discovered for this evergreen drug that remains a first-line treatment for several different inflammatory diseases. Due to its pleiotropic effects, this molecule is still of great interest in varied conditions, not exclusively inflammatory diseases. (2) Methods: The PubMed database was searched using combinations of the following keywords: dimethyl fumarate, pharmacokinetics, pharmacodynamics, adverse effects, psoriasis, multiple sclerosis, and clinical indications. This article reviews and updates the pharmacokinetics, mechanisms of action, and clinical indications of dimethyl fumarate. (3) Conclusions: The pharmacology of dimethyl fumarate is complex, fascinating, and not fully known. Progressive insights into the molecule's mechanisms of action will make it possible to maximize its clinical efficacy, reduce concerns about adverse effects, and find other possible areas of application.

SUBMITTER: Matteo P

PROVIDER: S-EPMC9788528 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

New and Old Horizons for an Ancient Drug: Pharmacokinetics, Pharmacodynamics, and Clinical Perspectives of Dimethyl Fumarate.

Matteo Paolinelli P Federico Diotallevi D Emanuela Martina M Giulia Radi R Tommaso Bianchelli B Alfredo Giacchetti G Anna Campanati C Annamaria Offidani O

Pharmaceutics 20221206 12

(1) Background: In their 60-year history, dimethyl fumarate and other salts of fumaric acid have been used for the treatment of psoriasis and other immune-mediated diseases for their immune-modulating properties. Over the years, new mechanisms of action have been discovered for this evergreen drug that remains a first-line treatment for several different inflammatory diseases. Due to its pleiotropic effects, this molecule is still of great interest in varied conditions, not exclusively inflammat ...[more]

PMID: 36559226

Similar Datasets

Project description:Background and Objective Based on basic knowledge and prior research on nitric oxide (NO), the potential of NO for treating eye diseases is reviewed, and the possibility of NO-based eye drops in clinical practice and the future potential of NO in ophthalmology are discussed. Methods A PubMed search was performed for English-language original reports and reviews using the following key words: nitric oxide, eye, ocular, and drug. Key Content and Findings NO is synthesized in the human body by NO synthase (NOS) from L-arginine or through enzyme-dependent reduction of dietary nitrate. Three types of NOS (eNOS, nNOS, and iNOS) are abundantly expressed in the eye under normal physiologic or pathologic conditions. The biological effect of NO in the eye is dose dependent. Low intraocular NO concentrations, produced by eNOS or nNOS, have various cellular effects, including vasodilation, intraocular pressure (IOP) regulation, and neuroprotection. iNOS induced under pathologic ocular conditions produces high NO concentrations in the local environment and mediates tissue inflammation, ocular cell apoptosis, and neurodegeneration. In particular, increased iNOS has been reported in glaucoma and retinal ischemic or degenerative diseases. NO plays a vital role in ocular injury. NO can facilitate ocular surface wound healing while eradicating pathogens such as bacteria and Acanthamoeba in chemical burns or infectious keratitis. Furthermore, NO has antifibrotic activity via the cyclic guanosine monophosphate (cGMP) signaling pathway. NO causes smooth muscle relaxation, which can be used to inhibit myopia progression in children. NO can be a stem cell modulator and may help in treating ocular stem cell disorders. Conclusions Because of its diverse biologic effects, NO can be a key player in regulating ocular inflammation in various ocular diseases, aiding ocular surface wound healing, controlling IOP in glaucoma, alleviating retinal disease, and suppressing myopia progression. Although there remain limitations to the effective use of highly unstable state, gaseous NO, the role of NO in the field of ophthalmology can be greatly expanded through the development of novel NO donors and effective delivery platforms.

Project description:BackgroundTecfidera® (dimethyl fumarate [DMF]) is an approved product for the treatment of relapsing forms of multiple sclerosis. Monomethyl fumarate (MMF) is the only active metabolite of DMF and is responsible for its therapeutic efficacy.ObjectiveThe objective of this study was to determine whether two Bafiertam™ capsules each containing 95 mg of MMF is bioequivalent to one Tecfidera® capsule containing 240 mg of DMF, a prodrug of MMF.MethodsThis was a single-dose, open-label, randomized, two-way crossover study evaluating two treatments over two periods with a washout interval between treatments. Fifty healthy subjects were randomized to receive a single dose of the test drug MMF 190 mg as 2 × 95 mg delayed-release capsules or the reference drug DMF 240 mg as a 1 × 240-mg delayed-release capsule. Blood samples were obtained prior to dosing and at prespecified time points through 24 h post-dose to determine plasma concentrations of MMF. The pharmacokinetic parameters of MMF were calculated including maximum observed concentration, time to reach maximum observed concentration, apparent half-life of the drug in plasma, AUC0-t which is the area under the plasma concentration-time curve (AUC) from time zero (dosing time) to the last time point, t, with measurable analyte concentration, and AUC0-inf, which is AUC0-t plus the extrapolated AUC from time t to infinity.ResultsThe geometric least-squares mean ratios (90% confidence interval) of the test drug MMF vs the reference drug DMF were 96.80% (92.18-101.64), 96.35% (91.81-101.12), and 104.84% (95.54-115.05) for AUC0-t, AUC0-inf, and maximum observed concentration, respectively. Two capsules of Bafiertam™ was safe and generally well tolerated. The most common adverse event for both products was flushing, 60% and 51%, for Bafiertam™ and Tecfidera®, respectively.ConclusionsBased on the statistical analysis results of the pharmacokinetic parameters of MMF, a single oral dose of two Bafiertam™ DR 95 mg capsules is bioequivalent to a single oral dose of one Tecfidera® DR 240 mg capsule.Clinical trial registrationThis study was retrospectively registered with ClinicalTrials.gov (NCT04570670) on 30 September, 2020.

Dataset Information

New and Old Horizons for an Ancient Drug: Pharmacokinetics, Pharmacodynamics, and Clinical Perspectives of Dimethyl Fumarate.

Publications

New and Old Horizons for an Ancient Drug: Pharmacokinetics, Pharmacodynamics, and Clinical Perspectives of Dimethyl Fumarate.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets