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• New generic and original brand-name S-1 products showed similar pharmacokinetics. • Safety profiles and tolerability of the new generic and original S-1 were adequate. • New generic and original S-1 were bioequivalent in cancer patients. • New generic S-1 product could be a cost-effective option for cancer treatment. S-1 is a multicomponent capsule containing tegafur, gimeracil, and oteracil potassium that has shown anticancer activity against numerous tumor types. However, S-1 capsules from different manufacturing companies have shown variations in pharmacokinetics and safety. Therefore, this multicenter, single-dose, randomized-sequence, open-label, two-way, self-crossover study was conducted to evaluate the bioequivalence of a newly developed generic S-1 (New Times Pharmaceutical Co., Ltd., Shandong, China) and the original brand-name S-1 capsule (Taiho Pharmaceutical Co., Ltd., Japan). Furthermore, the safety profiles of both products were compared. A total of 70 patients with 18 types cancer including breast, lung, gastric, and colorectal recruited at 5 hospitals who were randomly and alternatively administered 50 mg of the reference and test S-1 with a 7-day interval. Plasma concentrations of tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP), oteracil potassium, and 5-fluorouracil were detected using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters, including maximum drug concentration (C max), time to achieve C max (T max), half-life (t 1/2 , area under the concentration-time curve from 0–time t (AUC 0–t), and AUC from 0–infinity (AUC 0–∞) were determined using non-compartmental analysis with DAS2.0 software. Bioequivalence of the reference and test S-1 was evaluated according to 90% confidence intervals (CIs) for ratios of AUC and C max of S-1. Adverse events were evaluated by monitoring symptoms, physical and laboratory examinations, electrocardiogram, and subject interviews. No significant difference was observed in plasma concentrations and pharmacokinetic profiles of tegafur, CDHP, oteracil potassium, or 5-fluorouracil (p > 0.05) among cancer patients treated with the reference or test S-1 formulation. The 90% CIs of C max , AUC 0–t , and AUC 0–∞ ratios were within the 80%–125% limit. The generic S-1 caused eight mild adverse events including liver dysfunction, diarrhea, nausea, fatigue, abnormal blood electrolytes, hyperglycemia, and dermal toxicity. Similarly, 18 mild adverse events were observed including dysarteriotony, diarrhea, nausea, fatigue, fever, hematotoxicity, abnormal blood electrolytes, hyperglycemia, dermal toxicity, and joint pain. There were no differences in the adverse event incidence between the two formulations. In conclusion, the newly developed generic S-1 showed similar pharmacokinetics to those of an original brand-name S-1 in cancer patients, thereby indicating bioequivalence. Furthermore, both treatments were well tolerated, suggesting that the cost-effective generic S-1 should be considered as a feasible option when treating patients. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Abstract: By using the monochromatic images and magnetograms obtained with the satellite Hinode, 35 pairs of bipolar moving magnetic features (MMFs) in sunspot penumbrae are studied in the following three aspects: the morphological characteristics, velocities of motion and responses in low atmospheric layers. Then the following conclusions are drawn. (1) The bipolar MMFs appear in pairs of positive and negative polarities, are located in the midst of the approximately vertical magnetic fields in spot penumbrae, and move toward the outer boundaries of penumbrae. This indirectly justifies that the bipolar MMFs originate in the horizontal magnetic fields of penumbrae. In the time intervals of 2-8 hours and at the same positions, there appear the bipolar MMFs with similar morphologial characteristics and velocities of motion. This povides an evidence which supports the model of magnetic lines in the shape of sea serpent. (2) In the process of motion of bipolar MMFs there may appear brightenings in the photospere and chromosphere, and this implies that the middle and low layers of solar atmosphere are heated by the bipolar MMFs. (3) The sites of occurrence of bipolar MMFs and the distribution of penumbral magnetic field agree with the structural characteristics of uncombed sunspot penumbrae. [Copyright &y& Elsevier]