Novel mimetic tissue standards for precise quantitative mass spectrometry imaging of drug and neurotransmitter concentrations in rat brain tissues.

Understanding the relationship between the concentration of a drug and its therapeutic efficacy or side effects is crucial in drug development, especially to understand therapeutic efficacy in central nervous system drug, quantifying drug-induced site-specific changes in the levels of endogenous metabolites, such as neurotransmitters. In recent times, evaluation of quantitative distribution of drugs and endogenous metabolites using matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry imaging (MSI) has attracted much attention in drug discovery research. However, MALDI-MSI quantification (quantitative mass spectrometry imaging, QMSI) is an emerging technique, and needs to be further developed for practicable and convenient use in drug discovery research.

Highlights of the 14th Japan Bioanalysis Forum Symposium.

The 14th Japan Bioanalysis Forum Symposium was held at Tower Hall Funabori, Japan from 1-3 March 2023. The conference theme, 'Bringing Together - the Expertise of Bioanalysis', aimed to enable people from various fields to gather, learn and collaborate together for the common goal of delivering medicines to patients faster. Approximately 360 participants from various fields, including pharmaceutical industries, contractors, academia and regulatory authorities, gathered at an in-person symposium which had an online participation option, for the first time in 4 years.

Effects of microsampling on toxicity assessment of hematotoxic compounds in a general toxicity study in rats.

Microsampling (MS) has been increasingly used in toxicity studies reducing animal use for toxicokinetic analysis. However, especially for drugs with hematotoxic properties, the potential effects of MS on hematological parameters and subsequent toxicity assessment should be considered, while such properties are frequently unknown at the discovery stage. Here, we conducted a rat 2-week study of hematotoxic compounds and evaluated the effects of MS on toxicity assessment.

Multiplatform metabolomic analysis of the R6/2 mouse model of Huntington's disease.

Huntington's disease (HD) is a progressive, neurodegenerative disease characterized by motor, cognitive, and psychiatric symptoms. To investigate the metabolic alterations that occur in HD, here we examined plasma and whole-brain metabolomic profiles of the R6/2 mouse model of HD. Plasma and brain metabolomic analyses were conducted using capillary electrophoresis-mass spectrometry (CE-MS).

Pharmacokinetics, safety and metabolite profiling of minesapride, a novel 5-HT receptor partial agonist, in healthy elderly and young subjects.

Minesapride is a novel 5-hydroxytryptamine 4 (5-HT) receptor partial agonist that is expected to show efficacy in patients with irritable bowel syndrome with predominant constipation and functional constipation. An open-label study was conducted to evaluate pharmacokinetics (PK) and safety of minesapride. Japanese subjects, 12 elderly and 12 young, received a single oral dose of minesapride 40 mg/day in the fasted state.

Predicting Lifetime Transition Risk of Severe Visual Field Defects Using Monte Carlo Simulation in Japanese Patients with Primary Open-Angle Glaucoma.

Purpose: To maintain visual fields and quality of life over a lifetime, medical practice must be conducted taking into consideration not only visual field progression but also future visual field changes that occur over the patients' expected lifespan. The purpose of this study is to investigate the feasibility of establishing a model that predicts prognosis, estimating the proportion of glaucoma patients with severe visual field defects.

Patients And Methods: The data of 191 patients with primary open-angle glaucoma, with a predominance of normal-tension glaucoma, were used for this study.

Prediction methods of drug-drug interactions of non-oral CYP3A4 substrates based on clinical interaction data after oral administrations - Validation with midazolam, alfentanil, and verapamil after intravenous administration and prediction for blonanserin transdermal patch.

Drug-drug interactions (DDI) have been examined for various drugs for oral use, but less for non-oral applications. This study provides DDI prediction methods for non-orally administered CYP3A4 substrates based on clinical DDI data of oral dosages. Gut availability (F) and fraction contribution of CYP3A4 to hepatic intrinsic clearance (fm) were predicted by AUC ratio (AUCR) in oral DDI study with/without grapefruit juice, and alteration in intrinsic clearances with/without ketoconazole, respectively.

Correction to: Multicenter, Randomized, Controlled Study Comparing Tafluprost/Timolol Fixed Combination with Latanoprost/Timolol Fixed Combination in Primary Open-Angle Glaucoma and Ocular Hypertension.

In the original publication, the range to derive the P values is incorrectly represented in Table 2 and Table 3. The corrected tables are provided below.

Ocular hypotensive effects of prostaglandin analogs in Japanese patients with normal-tension glaucoma: a literature review.

Purpose: This paper aimed to evaluate the intraocular pressure (IOP)-lowering effects of prostaglandin analogs (PGAs) in Japanese patients with normal-tension glaucoma (NTG) by reviewing the current literature.

Methods: In February 2018, database searches were performed in PubMed, Embase, ProQuest, and the Japanese databases JAPICDOC and JMEDPlus. Studies were sorted into two categories: Category 1 consisted of studies of patients with NTG who reported reduced IOP values and Category 2 consisted of studies of patients with NTG who had IOP values at predosing and a final evaluation point.

Effect of quantitative intraocular pressure reduction on visual field defect progression in normal tension glaucoma under medical therapy applying Markov model.

Purpose: To quantitatively evaluate the association of intraocular pressure (IOP) reduction with visual field defect (VFD) progression in normal tension glaucoma (NTG) under medical therapy.

Patients And Methods: Clinical data for 622 eyes of 311 primary open-angle glaucoma and NTG patients were collected from April 2006 to March 2016. Of these patients, those with normal IOP, glaucomatous VFD by Anderson's criteria, corrected visual acuity ≥0.

Multicenter, Randomized, Controlled Study Comparing Tafluprost/Timolol Fixed Combination with Latanoprost/Timolol Fixed Combination in Primary Open-Angle Glaucoma and Ocular Hypertension.

Introduction: This was the first exploratory randomized controlled study to compare the efficacy and safety of a preserved tafluprost/timolol fixed combination (TAF/TIM) with a preserved latanoprost/timolol fixed combination (LAT/TIM).

Methods: This prospective, randomized, open-label study was conducted in Japanese patients with primary open-angle glaucoma, including normal-tension glaucoma or ocular hypertension. Following a 4-week LAT/TIM run-in period, eligible patients entered a 12-week treatment period, during which they received either LAT/TIM or TAF/TIM.

The 24-hour intraocular pressure control by tafluprost/timolol fixed combination after switching from the concomitant use of tafluprost and timolol gel-forming solution, in patients with primary open-angle glaucoma.

Objective: The aim of this study was to evaluate the 24-hour intraocular pressure (IOP)-control effect of the tafluprost/timolol fixed combination (TAF/TIM-FC) in patients with primary open-angle glaucoma after they switched from the concomitant use of tafluprost and timolol gel-forming solution.

Patients And Methods: Twenty patients with primary open-angle glaucoma (12 male and 8 female; mean ± SD age, 57.0±7.

Long-term progression of visual field defects and related factors in medically treated normal tension glaucoma.

Purpose: To analyze factors related to long-term progression of visual field defects (VFD) in patients with normal tension glaucoma (NTG) under medical therapy.

Patients And Methods: Clinical data from 622 eyes of 311 primary open-angle glaucoma and NTG patients were collected from April 2006 to March 2016. Of these patients, those with normal intraocular pressure (IOP); glaucomatous VFD judged by Anderson's criteria; corrected visual acuity ≥0.

Preperimetric Glaucoma Prospective Study (PPGPS): Predicting Visual Field Progression With Basal Optic Nerve Head Blood Flow in Normotensive PPG Eyes.

Purpose: To investigate the site specificity of visual field changes in eyes with normotensive preperimetric glaucoma (PPG), and to determine factors influencing visual field progression.

Methods: This prospective study comprised 84 eyes of 84 normotensive PPG patients followed for at least 16 months. Optic nerve head (ONH) blood flow was assessed with tissue-area mean blur rate (MBR), derived from laser speckle flowgraphy.

Preperimetric Glaucoma Prospective Observational Study (PPGPS): Design, baseline characteristics, and therapeutic effect of tafluprost in preperimetric glaucoma eye.

Purpose: There is no consensus on the diagnosis or treatment policy for Preperimetric Glaucoma (PPG) because the pathogenesis of PPG is not clear at this time. Preperimetric Glaucoma Prospective Observational Study (PPGPS) is a first multicenter, prospective, observational study to clarify the pathogenesis of PPG. This article indicates study design, patient baseline characteristics, and analysis focused on optic nerve head (ONH) blood flow in PPG, as well as the intraocular pressure (IOP) -lowering effect and ONH blood flow-improving effects of Tafluprost.

Prediction of Visual Field Progression in Patients with Primary Open-Angle Glaucoma, Mainly Including Normal Tension Glaucoma.

An objective method to predict individual visual field progression will contribute to realise personalised medication. The purpose of this study was to establish a predictive formula for glaucomatous visual field progression in patients with Primary open-angle glaucoma, mainly including normal tension glaucoma. This study was a large-scale, longitudinal and retrospective study including 498 eyes of 312 patients visiting from June 2009 to May 2015.

Effects of N-acetyltransferase 2 (NAT2), CYP2E1 and Glutathione-S-transferase (GST) genotypes on the serum concentrations of isoniazid and metabolites in tuberculosis patients.

For the purpose of a side-effect monitoring of isoniazid (INH), we investigated the relationship between the genotypes of drug-metabolizing enzymes involved in INH metabolism and the serum concentrations of INH and its metabolites in 129 tuberculosis patients hospitalizing in the National Hospital Organization Chiba-East Hospital. Genotype distributions of N-acetyltransferase 2 (NAT2), CYP2E1*5B, CYP2E1*6, Glutathione-S-transferase (GST) M1 and GST T1 were similar to those already reported in Japanese populations. Acetylating pathway of INH to acetyl isoniazid (AcINH) tended to shift to the hydrolytic pathway generating hydrazine (Hz) with the increase of mutant alleles in NAT2 gene.