Bioequivalence Dissolution Test Criteria for Formulation Development of High Solubility-Low Permeability Drugs.

The purpose of the present study was to provide the experimental and theoretical basis of bioequivalence (BE) dissolution test criteria for formulation development of high solubility-low permeability drugs. According to the biowaiver scheme based on the biopharmaceutics classification system (BCS), for BCS class III drugs, a test formulation and a reference formulation are predicted to be BE when 85% of the drug dissolves within 15 min (T < 15 min) in the compendial dissolution test. However, previous theoretical simulation studies have suggested that this criterion may possibly be relaxed for use in practical formulation development.

Prediction of Oral Drug Absorption in Rats from In Vitro Data.

Purpose: In drug discovery, rats are widely used for pharmacological and toxicological studies. We previously reported that a mechanism-based oral absorption model, the gastrointestinal unified theoretical framework (GUT framework), can appropriately predict the fraction of a dose absorbed (Fa) in humans and dogs. However, there are large species differences between humans and rats.

Preoperative CT Findings for Predicting Acute Exacerbation of Interstitial Pneumonia After Lung Cancer Surgery: A Multicenter Case-Control Study.

Acute exacerbation (AE) is a life-threatening complication of inter-stitial pneumonia (IP). Thoracic surgery may trigger AE. The purpose of this study is to explore the role of preoperative CT findings in predicting postoperative AE in patients with IP and lung cancer.

Bottom-Up Physiologically Based Oral Absorption Modeling of Free Weak Base Drugs.

In this study, we systematically evaluated "bottom-up" physiologically based oral absorption modeling, focusing on free weak base drugs. The gastrointestinal unified theoretical framework (the GUT framework) was employed as a simple and transparent model. The oral absorption of poorly soluble free weak base drugs is affected by gastric pH.

Titania Nanofilms from Titanium Complex-Containing Polymer Langmuir-Blodgett Films.

This paper proposes a method of fabricating low-dimensional TiO nanofilms at room temperature under ambient pressure conditions. The titanium-containing polymer complex Ti-p(DDA/acac) was synthesized by reacting an amphiphilic copolymer (p(DDA/acac)) with a titanium complex. Its ultrathin films were prepared using the Langmuir-Blodgett (LB) technique.

Prediction Characteristics of Oral Absorption Simulation Software Evaluated Using Structurally Diverse Low-Solubility Drugs.

The purpose of the present study was to characterize current biopharmaceutics modeling and simulation software regarding the prediction of the fraction of a dose absorbed (Fa) in humans. As commercial software products, GastroPlus™ and Simcyp® were used. In addition, the gastrointestinal unified theoretical framework, a simple and publicly accessible model, was used as a benchmark.

Harmonizing solubility measurement to lower inter-laboratory variance - progress of consortium of biopharmaceutical tools (CoBiTo) in Japan.

The purpose of the present study was to harmonize the protocol of equilibrium solubility measurements for poorly water-soluble drugs to lower inter-laboratory variance. The "mandatory" and "recommended" procedures for the shake-flask method were harmonized based on the knowledge and experiences of each company and information from the literature. The solubility of model drugs was measured by the harmonized protocol (HP) and the non-harmonized proprietary protocol of each company (nonHP).

18F-FDG uptake in the normal appendix in adults: PET/CT evaluation.

Objective: This study aimed to determine the level of F fluorodeoxyglucose (F-FDG) activity in the normal adult appendix using positron emission tomography/computed tomography (PET/CT).

Materials And Methods: We performed a retrospective review of PET/CT images using F-FDG in 563 consecutive asymptomatic adult patients without appendiceal pathology. We excluded 257 patients for an undetected or obscured appendix and three patients for appendicitis found on CT imaging.

Pemetrexed-induced scleroderma-like conditions in the lower legs of a patient with non-small cell lung carcinoma.

Pemetrexed, which is used for the treatment of non-small cell lung carcinoma and malignant mesothelioma, induces cutaneous adverse reactions in approximately 20% of patients. There are also reports of the induction of fibrosing disorders. We describe a case of pemetrexed-induced scleroderma-like conditions in the lower legs of a patient whose pulmonary carcinoma has been relatively well controlled, with prolongation of the dose interval, in spite of the discomfort in both his legs.

A clinically attainable dose of L-asparaginase targets glutamine addiction in lymphoid cell lines.

L-asparaginase (L-ASNase) is an important branch of chemotherapy for acute lymphoblastic leukemia (ALL) and some types of non-Hodgkin's lymphoma, including natural killer (NK)-cell lymphoma. Although it mediates hydrolysis of asparagine (Asn) and glutamine (Gln), which are variably required for cancer cell survival, the relative contribution of Asn and Gln depletion to the anti-tumor activity in therapeutic doses is unclear in ALL and malignant lymphoma. Here we demonstrate that L-ASNase exerts cytotoxicity through targeting the Gln addiction phenotype in lymphoid cell lines.

Chest HRCT findings in acute transformation of adult T-cell lymphoma/leukemia.

Objectives: To assess chest high-resolution computed tomography (HRCT) findings in patients with acute transformation of adult T cell leukaemia/lymphoma (ATLL).

Methods: We retrospectively identified 72 consecutive patients at our institution with ATLL between October 2000 and March 2014. The cases included acute type (n = 20), lymphoma type (n = 21), smouldering type (n = 24) and chronic type (n = 7).

Application of the BCS biowaiver approach to assessing bioequivalence of orally disintegrating tablets with immediate release formulations.

The aim of this study was to compare the dissolution profiles of oral disintegrating tablets (ODTs) and immediate release (IR) formulations in order to experimentally validate the regulatory biowaiver scheme (BWS) for biopharmaceutical classification system (BCS) class III drugs. We examined six drugs that show clinical bioequivalence between the ODTs and IR formulations: taltirelin, olopatadine, droxidopa, famotidine, fexofenadine, and hydrochlorothiazide. The dissolution profiles of these drugs were evaluated using the compendium paddle apparatus at pH 1.

Comparison of high-resolution computed tomography findings between Pseudomonas aeruginosa pneumonia and Cytomegalovirus pneumonia.

Objective: To compare pulmonary high-resolution CT (HRCT) findings in patients with Pseudomonas aeruginosa pneumonia to HRCT findings in patients with Cytomegalovirus (CMV) pneumonia.

Methods: We studied 124 patients (77 men, 47 women; age range, 20-89 years; mean age, 65.4 years) with P.

Evaluation of microscopic tumor extension in early-stage cervical cancer: quantifying subclinical uncertainties by pathological and magnetic resonance imaging findings.

We performed a detailed analysis of hysterectomy specimens of uterine cervical cancer to determine the appropriate length of uterine body to include within the clinical target volume. Between 2008 and 2011, 54 patients with uterine cervical carcinoma underwent hysterectomy. Those with quality pre-operative magnetic resonance imaging (MRI) data were included for analysis.

Association of computed tomography-detected pulmonary interstitial changes with severe radiation pneumonitis for patients treated with thoracic radiotherapy.

We evaluated associations of interstitial changes with radiation pneumonitis (RP) for patients treated with thoracic radiotherapy. Between 2005 and 2009, patients who received thoracic radiotherapy of 40 Gy or more for lung cancer or thymic tumors and were followed-up for more than 6 months were eligible for this study. Possible risk factors for RP included the presence of interstitial changes on computed tomography before radiotherapy, and elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH) levels; these were compared with the incidences of severe RP.

Clinical and pulmonary thin-section CT findings in acute Klebsiella pneumoniae pneumonia.

The aim of this study was to assess the clinical and pulmonary thin-section CT findings in patients with acute Klebsiella pneumoniae pneumonia. We retrospectively evaluated thin-section CT examinations performed between January 1991 and December 2007 from 962 patients with acute Klebsiella pneumoniae pneumonia. Seven hundred and sixty-four cases with concurrent infectious diseases were excluded.

Elucidation of the mode of interaction in the UP1-telomerase RNA-telomeric DNA ternary complex which serves to recruit telomerase to telomeric DNA and to enhance the telomerase activity.

We found that UP1, a proteolytic product of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), both enhances and represses the telomerase activity. The formation of the UP1-telomerase RNA-telomeric DNA ternary complex was revealed by a gel retardation experiment. The interactions in the ternary and binary complexes were elucidated by NMR.

Clinical/pathologic correlations in 553 patients with primary centrilobular findings on high-resolution CT scan of the thorax.

Background: Clinical/pathologic correlations in patients with high-resolution CT (HRCT) scan findings presenting with two patterns of centrilobular opacity remain unclear.

Methods: Chest HRCT scans in 553 patients with predominant centrilobular opacities or preferential centrilobular disease were retrospectively evaluated. In 141 patients who underwent biopsy, CT scan images were compared with actual specimens.

Pulmonary computed tomography findings of visceral larva migrans caused by Ascaris suum.

Objective: To retrospectively evaluate the computed tomography (CT) findings of pulmonary involvement in patients with visceral larva migrans caused by Ascaris suum.

Methods: Institutional review board approval was obtained, and informed consent was waived. Chest CT scans obtained between January 1994 and November 2005 in 32 patients infected with A.