Exposure-response modeling of peficitinib efficacy in patients with rheumatoid arthritis.

The aim was to analyze the relationship between peficitinib exposure and efficacy response according to American College of Rheumatology (ACR) 20 criteria and 28-joint disease activity score based on C-reactive protein (DAS28-CRP) in rheumatoid arthritis (RA) patients, and to identify relevant covariates by developing exposure-response models. The analysis incorporated results from three multicenter, placebo-controlled, double-blind studies. As an exposure parameter, individual post hoc pharmacokinetic (PK) parameters were obtained from a previously constructed population PK model.

Population pharmacokinetic analysis of peficitinib in patients with rheumatoid arthritis.

Aims: To analyse the population pharmacokinetics (PK) of peficitinib in patients with rheumatoid arthritis (RA) and assess the potential PK covariates to identify the requirement for dose adjustment in RA patients.

Methods: The analysis incorporated 2464 observations from 98 healthy volunteers and 4919 observations from 989 RA patients. A population PK model for peficitinib in RA patients was constructed by a nonlinear mixed effect model using NONMEM with prior information from a healthy volunteer model.

The Bioequivalence of Two Peficitinib Formulations, and the Effect of Food on the Pharmacokinetics of Peficitinib: Two-Way Crossover Studies of a Single Dose of 150 mg Peficitinib in Healthy Volunteers.

The marketed tablet formulation of peficitinib differs from the tablet used during the clinical trials. The bioequivalence of the marketed formulation and developmental tablet, and the food effect on the marketed formulation, were analyzed in 2 Japanese open-label, randomized, 2-way crossover studies in healthy male volunteers. Volunteers received a single oral dose of the marketed 150-mg peficitinib tablet under fasted conditions (bioequivalence), and under fed or fasted conditions (food effect).

A drug-drug interaction study to evaluate the impact of peficitinib on OCT1- and MATE1-mediated transport of metformin in healthy volunteers.

Purpose: Peficitinib is an oral pan-Janus kinase inhibitor for the treatment of rheumatoid arthritis. Co-administration of peficitinib with metformin, a type 2 diabetes therapy, can occur in clinical practice. Hepatic and renal uptake of metformin is mediated by organic cation transporter 1 (OCT1) and OCT2, respectively, and its renal excretion by multidrug and toxin extrusion 1 (MATE1) and MATE2-K.

Pharmacokinetics, Pharmacodynamics, and Safety of Peficitinib (ASP015K) in Healthy Male Caucasian and Japanese Subjects.

Background And Objective: Peficitinib pharmacokinetics and pharmacodynamics have been characterized mainly in Caucasian subjects. This study investigated the pharmacokinetics, pharmacodynamics, safety, and tolerability of peficitinib in healthy Japanese subjects compared with Caucasian subjects.

Methods: In this single-center, randomized, double-blind, placebo-controlled study, a cohort of healthy Japanese (n = 24) and Caucasian (n = 24) men received a single oral dose of peficitinib (20, 60, or 200 mg) or placebo.

Pharmacokinetics and Safety of a Single Oral Dose of Peficitinib (ASP015K) in Japanese Subjects With Normal and Impaired Hepatic Function.

Peficitinib (ASP015K) is a novel Janus kinase inhibitor developed for the treatment of rheumatoid arthritis (RA). The impact of hepatic impairment on the peficitinib pharmacokinetic (PK) and safety profile was investigated in non-RA subjects (n = 24) in an open-label, parallel-group, multicenter comparative study in Japan. Subjects received a single, clinically relevant, oral dose of a peficitinib 150 mg tablet under fasting conditions.

Pharmacokinetics and Safety of a Single Oral Dose of Peficitinib (ASP015K) in Japanese Subjects with Normal and Impaired Renal Function.

Background And Objective: This study measured and compared the exposure and safety of peficitinib (ASP015K), a novel oral Janus kinase inhibitor, in subjects with normal and impaired renal function after a single oral, clinically relevant peficitinib dose.

Methods: This was an open-label, parallel-group study conducted at two centres in Japan. Subjects with normal and mildly, moderately, or severely impaired renal function received a single oral dose of peficitinib (one 150 mg tablet) under fasting conditions in a hospital setting.

Results of switchback from ranibizumab to aflibercept in patients with exudative age-related macular degeneration.

Purpose: Intravitreal injection of anti-VEGF drugs has become standard therapy for patients with exudative age-related macular degeneration (AMD). However, some patients do not exhibit sufficient response to the drugs for suppression of choroidal neovascularization activity. We investigated the efficacy of switchback from ranibizumab to aflibercept in patients with AMD who could not achieve further benefit beyond initial therapy of aflibercept injection.

Reduction of Intraocular Pressure by Additional Trabeculotomy Ab Externo in Eyes With Primary Open-angle Glaucoma.

Purpose: The purpose of this study was to determine whether a second trabeculotomy (LOT) can reduce the intraocular pressure (IOP) in eyes with primary open-angle glaucoma (POAG) that had undergone an unsuccessful LOT as the initial surgery.

Patients And Methods: LOT ab externo was performed as a second surgery on 37 eyes of 34 POAG patients who had undergone an unsuccessful LOT as the initial surgery. The main outcome measure was the postoperative IOPs, and surgical failures were defined as eyes with a post-LOT IOP>20 mm Hg.

Selegiline increases on time without exacerbation of dyskinesia in 6-hydroxydopamine-lesioned rats displaying l-Dopa-induced wearing-off and abnormal involuntary movements.

3,4-Dihydroxy-l-phenylalanine (l-Dopa) remains the most effective drug for treating the motor symptoms of Parkinson's disease (PD). However, its long-term use is limited due to motor complications such as wearing-off and dyskinesia. A clinical study in PD patients with motor complications has demonstrated that selegiline, a monoamine oxidase type B inhibitor, is effective in reducing off time without worsening dyskinesia, although another study has shown worsening dyskinesia.

Long-Term Stability of Minimally Invasive Radial Keratotomy for Mild to Moderate Keratoconus.

Purpose: This study aimed to evaluate the long-term stability of minimally invasive radial keratotomy (mini-RK) for eyes with mild to moderate keratoconus.

Design: Retrospective observational case series.

Methods: Eleven eyes from 6 patients with hard contact lens (HCL)-intolerant keratoconus underwent mini-RK and were followed up for more than 5 years.

Psychomotor effect differences between l-methamphetamine and d-methamphetamine are independent of murine plasma and brain pharmacokinetics profiles.

l-Methamphetamine has been occasionally referred to as a stimulant similar to d-methamphetamine, probably owing to insufficient comparative studies. Here, we directly compared psychomotor efficacies and pharmacokinetics of methamphetamine enantiomers in mice. Only d-methamphetamine, but not l-methamphetamine, induced stereotypy and sensitization at 1-10 mg/kg.

Drug Interactions Between Peficitinib, an Orally Administered, Once-Daily Janus Kinase Inhibitor, and Rosuvastatin in Healthy Subjects.

Background And Objective: Peficitinib is an orally administered, once-daily Janus kinase inhibitor in development for the treatment of rheumatoid arthritis. Peficitinib and its major metabolite H2 inhibit the hepatic uptake transporter organic anion transporting polypeptide 1B1 (OATP1B1) in vitro. This article reports a clinical study evaluating the effects of peficitinib on the pharmacokinetics of rosuvastatin, a substrate for the OATP1B1 transporter, and vice versa.

Case of Primary Intraocular Lymphoma with Extraocular Extension.

Purpose: To describe a case of primary intraocular lymphoma (PIOL) with an extension through the sclera that was confirmed to be part of the PIOL by histopathological examinations.

Case: An 89-year-old woman was referred to a local clinic with a 1-year history of persistent blurred vision in her left eye. After 2 years without aggressive treatments, she had a marked reduction of vision and pain in her left eye.

Three-year results of a modified photodynamic therapy procedure (Ironing PDT) for age-related macular degeneration patients with large lesions.

Background: To evaluate the effect of photodynamic therapy (PDT) using a modified procedure on exudative age-related macular degeneration having been conventionally difficult to treat.

Methods: The medical records of eight consecutive patients (eight eyes) with age-related macular degeneration treated with modified PDT were reviewed retrospectively. Modified PDT was used for the lesions that could not be covered by conventional use of PDT, either because the lesion was too large or too close to the optic disc.

Favorable anatomic and visual outcomes with 25-gauge vitrectomy for myopic foveoschisis.

Purpose: To report the surgical outcomes of 25-gauge vitrectomy in eyes with myopic foveoschisis (MF).

Methods: The medical records of 40 eyes of 36 patients that had undergone 25-gauge vitrectomy with internal limiting membrane peeling for MF were studied. The main outcome measures were the best-corrected visual acuity (BCVA) and the optical coherence tomography (OCT) findings.

Clinical features of diabetic patients referred by general physicians due to less ophthalmic examinations.

Background: The purpose of this study was to determine the clinical features of patients with type 2 diabetes, and less ophthalmic examinations, referred by general physicians to ophthalmologists.

Methods: The medical charts of 327 patients with type 2 diabetes referred to our department from general physicians were reviewed. A detailed medical history was taken and a complete ophthalmic examination was performed for all patients.

Usefulness of dual echo volumetric isotropic turbo spin echo acquisition (VISTA) in MR imaging of the temporomandibular joint.

Purpose: We investigated the ability to detect the articular disk and joint effusion of the temporomandibular joint (TMJ) of a method of dual echo volumetric isotropic turbo spin echo acquisition (DE-VISTA) additional fusion images (AFI).

Methods: DE-VISTA was performed in the 26 TMJ of 13 volunteers and 26 TMJ of 13 patients. Two-dimensional (2D) dual echo turbo spin echo was performed in the 26 TMJ of 13 volunteers.

Fever of unknown origin successfully treated by oren-gedoku-to (huanglian-jie-du-tang).

Oren-gedoku-to is a traditional medicine used for treating inflammatory conditions and is given by prescription in Japan, People's Republic of China, and Korea. Its anti-inflammatory effect is related to the arachidonate cascade and inhibition of cyclo-oxygenase, but research on other anti-inflammatory pathways is ongoing. We report a case of fever of unknown origin in a 33-year-old woman.

Initial non-responders to ranibizumab in the treatment of age-related macular degeneration (AMD).

Background: Patients with exudative age-related macular degeneration (AMD) who did not respond to ranibizumab at the induction phase were assessed and referred to as initial non-responders.

Methods: We retrospectively reviewed the medical records of 215 patients (218 eyes) with exudative AMD. For the initial treatments, patients received three intravitreal injections of ranibizumab (IVR) every 4 weeks.

Two cases of intraocular lymphoma diagnosed by analyses of vitreous and infusion fluid.

Purpose: Intraocular lymphomas are rare, and they have poor prognosis. Thus, early diagnosis and treatment are needed. A definitive diagnosis of a lymphoma is based on cytological analysis of the intraocular fluids or tissues.

A long-term follow-up of peripapillary retinoschisis with optic disc hypoplasia.

Peripapillary and macular retinoschisis are usually associated with optic disc pits. We report a rare case of peripapillary retinoschisis with optic disc hypoplasia. A 59-year-old woman presented with asthenopia.

Two cases of ocular sarcoidosis in which vitreous cytology was useful for supporting the diagnosis.

The purpose of this paper is to report two cases of sarcoidosis with conflicting signs in which vitreous cytology was useful for supporting the diagnosis. Case 1 was a 56-year-old man who was referred with blurred vision, and was found to have iridocyclitis, vitreous opacities, and optic neuritis bilaterally. He also had a swelling of both mandibular glands.

Population pharmacokinetic modeling of sepantronium bromide (YM155), a small molecule survivin suppressant, in patients with non-small cell lung cancer, hormone refractory prostate cancer, or unresectable stage III or IV melanoma.

Purpose Population pharmacokinetics (PK) of sepantronium bromide (YM155) was characterized in patients with non-small cell lung cancer, hormone refractory prostate cancer, or unresectable stage III or IV melanoma and enrolled in one of three phase 2 studies conducted in Europe or the U.S. Method Sepantronium was administered as a continuous intravenous infusion (CIVI) at 4.

Pharmacokinetics of sepantronium bromide (YM155), a small-molecule suppressor of survivin, in Japanese patients with advanced solid tumors: dose proportionality and influence of renal impairment.

Purpose: The purpose of this analysis was to investigate the pharmacokinetics (PK) of sepantronium (YM155), a small-molecule suppressor of the expression of the antiapoptosis protein survivin, in Japanese patients with advanced solid tumors and to evaluate the effect of renal impairment on the PK profile of sepantronium.

Methods: Sepantronium was administered as a continuous intravenous infusion of 1.8-10.