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This study aims to investigate the effect of Epstein–Barr virus (EBV) reactivation or EBV reactivation with dexamethasone (DXM) in patients with adverse drug reactions (ADRs) through evaluating the levels of monocyte, macrophage M2/M1, and cytokines, and investigating whether expression of EBV receptor EphA2 could specifically influence EBV activation in ADRs. We performed a prospective longitudinal study to analyze the monocytes, macrophages, M2/M1 ratio, and cytokines, including interleukin (IL)‐4, IL‐13, tumor necrosis factor (TNF)‐α, interferon (IFN)‐γ, IFN‐β, C‐X‐C motif chemokine ligand (CXCL)9, and CXCL10, in patients with maculopapular exanthema (MPE) and Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), and control groups after disease onset. Skin biopsy samples from these patients were subjected to hematoxylin and eosin (H&E) staining to examine tissue architecture and inflammatory cell infiltration, as well as Epstein–Barr virus‐encoded RNA (EBER) staining to detect the presence of EBV within the skin lesions. Peripheral blood mononuclear cells collected from these patients were co‐cultured with EBV or EBV combined with DXM to assess the impact on monocytes, macrophages, the M2/M1 ratio, and the associated cytokine profile. Furthermore, we sought to identify which cytokines might be crucial in mediating the interaction between the M2/M1 ratio and EBV. EPhA2 expression was evaluated to determine its role in the reactivation of EBV and its correlation with increased viral load in MPE and SJS/TEN patients. Selective depletion of macrophages occurred during the acute stage of SJS/TEN, while a shift towards M2 macrophages was observed in MPE. Both IFN‐β and CXCL9 levels were elevated in MPE and SJS/TEN. Additionally, our study demonstrated the presence of EBV in the skin lesions of SJS/TEN and MPE patients through H&E and EBER staining, confirming EBV's involvement in these conditions. Activation of EBV and EBV combined with DXM led to a shift from M1 to M2 macrophages, accompanied by increased levels of IL‐4, IFN‐γ, and CXCL9 in MPE and SJS/TEN, compared to healthy individuals. Specifically, EBV combined with DXM primarily drove IFN‐γ and IL‐4 expansions in MPE, while CXCL9 was predominantly elevated in SJS/TEN. The increased IL‐4 levels were associated with the relative rise in EBV viral loads after EBV combined with DXM stimulation. Furthermore, EphA2 expression in monocytes was significantly higher in SJS/TEN and MPE patients compared to controls, with further increases on EBV stimulation. This elevation in EPhA2 correlated with increased EBV viral load, particularly in MPE and SJS/TEN patients. The gradual shift from M1 to M2 cell development observed during the clinical course of MPE and SJS/TEN is mediated by the predominance of EBV and EBV with DXM at the acute stage, leading to elevated IL‐4, IFN‐γ, and CXCL9 levels, which may exacerbate allergic reactions. The elevation in EPhA2 correlated with increased EBV viral load, particularly in MPE and SJS/TEN patients, suggesting that adverse drug reactions may induce EPhA2 expression, facilitating EBV replication and activation. EphA2 could thus serve as an indicator of EBV activation and a marker for assessing the risk of EBV in patients with adverse drug reactions. [ABSTRACT FROM AUTHOR]

This bioequivalence study is critically important for drug production. Recently, a local pharmaceutical company produced esomeprazole magnesium enteric‐coated capsules, a major drug to help to eradicate Helicobacter pylori, but the bioequivalence is not well known. The present study aimed to evaluate the bioequivalence of the 2 esomeprazole magnesium enteric‐coated capsules and their pharmacokinetics and safety in 3 biological equivalence trials: fasting, feeding, and mixing. The fasting and mixing trials used single‐centered randomized, open‐label, single‐dose, 2‐treatment, 2‐period, and 2‐sequence crossover design, while the fed trials used single‐centered, randomized, open‐label, single‐dose, 2‐treatment, 3‐period, 3‐sequence partial crossover design. For the fasting and mixing trials, each of the 32 subjects was fasted overnight prior to taking the test preparations or reference preparations. In the fed trial, 54 subjects were given a high‐fat meal 1 hour before the drugs were administered. Blood specimens from all subjects were collected against the light within 14 hours, with the plasma drug concentration being detected by the validated ultra‐performance liquid chromatography–tandem mass spectrometry analysis method. Geometric mean ratio of maximum concentration, the area under the concentration–time curve from time zero to the last measurable concentration, and area under the concentration–time curve from time zero to infinity with 90% confidence interval were calculated. The data from fasting, mixing, and fed trials met the bioequivalence criteria. No serious adverse reactions were found, suggesting that the test and reference preparations of esomeprazole magnesium enteric capsules have similar safety profile. [ABSTRACT FROM AUTHOR]