Objective: In Japan, to prevent an increase in medical expenditure associated with development of super-aging society, the use of generic drugs is being promoted.  To help patients financially and meet their various other needs, generic drugs (e.g., orally disintegrating film formulations) whose dosage forms do not exist for original drugs are manufactured and distributed.  In this study, to evaluate the characteristics of an orally disintegrating film formulation, we performed dissolution, disintegration, and simulated intraoral tests of Amlodin® tablets 2.5 mg, Amlodin® OD tablets 2.5 mg, and Amlodipine OD film 2.5 mg that were manufactured by TEVA-KOWA PHARMA Co., Ltd.
Methods: Dissolution and disintegration tests were performed in line with the Japanese Pharmacopoeia, Sixteenth Edition, and the dose of amlodipine was determined by high-performance liquid chromatography.  During the simulated intraoral test, the tested drugs’ disintegration in purified water and artificial saliva was observed macroscopically, and recorded using a digital camera.
Results: Since the each formulation showed an over 85.0% rate of dissolution 15 min after the initiation of the dissolution test, no difference was found in elution behavior.  Also, in the simulated intraoral test, the film formulation began to disintegrate the earliest (2 and 10 min when using purified water and artificial saliva, respectively) among the tested drugs.
Conclusion: Our findings suggest that orally disintegrating film formulations show superior disintegration to uncoated or orally disintegrating tablets, and benefits on taking medicine was observed.

Little is known regarding the effects of mineral-containing supplemention on oxidative stress markers, carbohydrate and lipid metabolism in response to an acute bout of exercise in humans. The present study investigated whether prior mineral-containing supplemention can improve oxidative stress status and how this supplementation influences on carbohydrate and lipid metabolism after a single bout of cycling in young men. Twelve, healthy young men (aged 22.5 ± 2.4 years, mean ± SD) underwent two, 150-min trials in a random order. Each participant received oral administration of mineral supplement containing 13.4 mg of sulphur or placebo one minute before exercise. In both trials, participants cycled at 75% of heart rate reserve for 60 minutes and then rested for 90 minutes. Blood samples were collected pre-exercise supplementation, immediately after exercise, 30 minutes after exercise, 60 minutes after exercise and 90 minutes after exercise. Circulating concentrations of derivatives of reactive oxygen metabolites, biological antioxidant potential, glucose and insulin did not differ between trials. Elevated circulating concentrations of non-esterified fatty acids were observed immediately after exercise in the supplementation trial compared with the placebo trial (mean ± SD: 1.1 ± 0.5 and 0.9 ± 0.3 mmol/L, respectively: trial × time interaction, p = 0.036). The present study showed that acute mineral-containing antioxidant supplemention appears to have no effect on improving oxidative stress markers in response to a single bout of cycling in healthy young men. In addition, the findings of this study suggested that mineral-containing supplemention may influence lipids metabolism during exercise.

Objective: In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression. Methods: Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events. Results: Between February 2018 and September 2020, 99 patients were enrolled; of these, 82patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase). Conclusion The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE.Trial Registration: JRCT Identifier: jRCTs031180124

Objective: In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression. Methods: Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events. Results: Between February 2018 and September 2020, 99 patients were enrolled; of these, 82patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase). Conclusion The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE.Trial Registration: JRCT Identifier: jRCTs031180124

Objective: In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression. Methods: Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events. Results: Between February 2018 and September 2020, 99 patients were enrolled; of these, 82patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase). Conclusion The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE.Trial Registration: JRCT Identifier: jRCTs031180124

Introduction: The diagnosis of cancer-related neuropathic pain is often difficult for non-pain medicine specialists. We examined whether a Japanese version of a neuropathic pain screening questionnaire (Japan-Q), which was developed for chronic pain, is appropriate for screening cancer-related neuropathic pain. Methods: Our palliative care team screened 104 patients from May 2014 to December 2015 and compared total points of the Japan-Q with diagnosis of the type of cancer pain by specialized pain clinicians. Validity was evaluated using a receiver operating characteristic (ROC) curve. Results: The area under the ROC curve in terms of the total score, sensitivity, and specificity for the Japan Q was 0.82, which indicated a moderate level of diagnostic accuracy. A cut-off value of 3 points was shown to be best (sensitivity: 79%, specificity: 82%). When a cut-off value of 9 points was used as the diagnostic criterion for neuropathic pain, there was greatly reduced sensitivity (sensitivity: 40%, specificity: 97%). Conclusion: Although the Japan-Q shows moderate diagnostic accuracy related to cancer pain, the cut-off value for this tool is lower than that for chronic pain. Cancer-related neuropathic pain should be suspected with a total score of 3 or more in the Japan-Q.