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Voriconazole is a second‐generation, synthetic, triazole antifungal drug based on the structure of fluconazole. We compared the safety, tolerability, and pharmacokinetic characteristics of voriconazole for injection (200 mg) manufactured by at a dose of 6 mg/kg in Chinese healthy adult volunteers. This was a single‐center, randomized, open, 2‐preparation, single‐dose, 2‐period, 2‐sequence, crossover bioequivalence clinical trial. Twenty‐four eligible, healthy, male, and female volunteers were assigned randomly to one of 2 dose‐sequence groups (test‐reference group or reference‐test group) in a 1:1 block. The voriconazole concentration in plasma was determined by protein precipitation and high‐performance liquid chromatography‐tandem mass spectrometry. The main PK parameters were calculated on the basis of a noncompartmental model. The ratio of the geometric mean of the maximum plasma drug concentration, area under the plasma concentration–time curve from time 0 to the last time of quantifiable concentration, and area under the plasma concentration‐time curve from time 0 to infinity of the test preparation, and the reference preparation was 100.4%, 102%, and 102.2%, respectively. The 90% confidence intervals were between 80% and 125%, indicating that the 2 preparations were bioequivalent. The adverse events experienced by healthy adult volunteers were mild. Both preparations had a good safety profile. [ABSTRACT FROM AUTHOR]

Diverse extraintestinal diseases are characterized by localized inflammatory responses and tissue damage, accompanied with intestinal inflammation and injury. Here, a dual-functionality and dual-location intervention strategy is reported, which is the use of hyaluronic acid-nanocoated Clostridium butyricum to generate an anti-inflammatory tissue-repair effect in the impaired gut and extraintestinal organs. Nanocoated bacteria attenuate intestinal mucosal inflammation and recover gut barrier integrity by leveraging the immunosuppressive nature of hyaluronic acid and the butyrate-producing ability of Clostridium butyricum. Nanocoated bacteria also alleviate the interstitial inflammation and pathological damage of extraintestinal organs via remodeling microbial metabolites and decreasing microbial translocation. In murine models of acute kidney injury and chronic kidney disease, oral delivery of nanocoated bacteria demonstrates the potency to restore renal function and eliminate renal fibrosis. This work proposes a type of next-generation living therapeutics for treating extraintestinal diseases., (© 2024 Wiley‐VCH GmbH.)

Background: A preoperative diagnosis to distinguish malignant from benign thyroid nodules accurately and sensitively is urgently important. However, existing clinical methods cannot solve this problem satisfactorily. The aim of this study is to establish a simple, economic approach for preoperative diagnosis in eastern population., Methods: Our retrospective study included 86 patients with papillary thyroid cancer and 29 benign cases. The ITK-SNAP software was used to draw the outline of the area of interest (ROI), and Ultrosomics was used to extract radiomic features. Whole-transcriptome sequencing and bioinformatic analysis were used to identify candidate genes for thyroid nodule diagnosis. RT-qPCR was used to evaluate the expression levels of candidate genes. SVM diagnostic model was established based on the METLAB 2022 platform and LibSVM 3.2 language package., Results: The radiomic model was first established. The accuracy is 73.0%, the sensitivity is 86.1%, the specificity is 17.6%, the PPV is 81.6%, and the NPV is 23.1%. Then, CLDN10, HMGA2, and LAMB3 were finally screened for model building. All three genes showed significant differential expressions between papillary thyroid cancer and normal tissue both in our cohort and TCGA cohort. The molecular model was established based on these genetic data and partial clinical information. The accuracy is 85.9%, the sensitivity is 86.1%, the specificity is 84.6%, the PPV is 96.9%, and the NPV is 52.4%. Considering that the above two models are not very effective, We integrated and optimized the two models to construct the final diagnostic model (C-thyroid model). In the training set, the accuracy is 96.7%, the sensitivity is 100%, the specificity is 93.8%, the PPV is 93.3%, and the NPV is 100%. In the validation set, the accuracy is 97.6%, the sensitivity remains 100%, the specificity is 84.6%, the PPV is 97.3%, and the NPV is 100%., Discussion: A diagnostic panel is successfully established for eastern population through a simple, economic approach using only four genes and clinical data., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Dai, Lin, Zhang, Wen, Chen, Li, You, Qu, Ni and Cai.)

Purpose: The aim of this study was to evaluate the bioequivalence of two formulations of rupatadine (10-mg tablets) under fasting and fed conditions in healthy Chinese subjects., Methods: A total of 72 subjects were randomly assigned to the fasting cohort ( n = 36) and fed cohort ( n = 36). Each cohort includes four single-dose observation periods and 7-day washout intervals. Blood samples were collected at several timepoints for up to 72 h post-dose. The plasma concentration of rupatadine and the major active metabolites (desloratadine and 3-hydroxydesloratadine) were analyzed by a validated HPLC-MS/MS method. The non-compartmental analysis method was employed to determine the pharmacokinetic parameters. Based on the within-subject standard deviation of the reference formulation, a reference-scaled average bioequivalence or average bioequivalence method was used to evaluate the bioequivalence of the two formulations., Results: For the fasting status, the reference-scaled average bioequivalence method was used to evaluate the bioequivalence of the maximum observed rupatadine concentration (C max ; subject standard deviation > 0.294), while the average bioequivalence method was used to evaluate the bioequivalence of the area under the rupatadine concentration-time curve from time 0 to the last detectable concentration (AUC 0-t ) and from time 0 to infinity (AUC 0-∞ ). The geometric mean ratio (GMR) of the test/reference for C max was 95.91%, and the upper bound of the 95% confidence interval was 95.91%. For AUC 0-t and AUC 0-∞ comparisons, the GMR and 90% confidence interval (CI) were 98.76% (93.88%-103.90%) and 98.71% (93.93%-103.75%), respectively. For the fed status, the subject standard deviation values of C max , AUC 0-t , and AUC 0-∞ were all <0.294; therefore, the average bioequivalence method was used. The GMR and 90% CI for C max , AUC 0-t , and AUC 0-∞ were 101.19% (91.64%-111.74%), 98.80% (94.47%-103.33%), and 98.63% (94.42%-103.03%), respectively. The two-sided 90% CI of the GMR for primary pharmacokinetic endpoints of desloratadine and 3-hydroxydesloratadine was also within 80%-125% for each cohort. These results met the bioequivalence criteria for highly variable drugs. All adverse events (AEs) were mild and transient., Conclusion: The test drug rupatadine fumarate showed a similar safety profile to the reference drug Wystamm ® (J. Uriach y Compañía, S.A., Spain), and its pharmacokinetic bioequivalence was confirmed in healthy Chinese subjects based on fasting and postprandial status., Clinical Trial Registration: http://www.chinadrugtrials.org.cn/index.html, identifier CTR20213217., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lin, Lou, Hao, Shao, Yu, Fang, Bao, Yi and Zhang.)