To assess the food effects and pharmacokinetic profile of oral prednisone (test preparation,5 mg) and prednisolone tablets (reference preparation,5 mg) using a randomized, two-period, two crossover, single-dose, fast and fed trial in 48 (24 in fast, 24 in fed) healthy Chinese adult subjects. In the trial, the plasma concentrations were determined at different time points up to 24 h and the pharmacokinetic parameters were analyzed according to the concentration data by non-compartmental analysis using WinNonlin software. All laboratory parameters, vital signs and adverse events (AEs) were monitored and recorded under the supervision of the clinicians throughout the whole process of the study. Prednisone and prednisolone undergo interconversion in liver. On average, the bioavailability of prednisolone after oral prednisone is approximately 80 http://www.chinadrugtrials.org.cn/ at 11 March 2020. • The food effects and pharmacokinetic evaluation of prednisone acetate and prednisolone were investigated in healthy Chinese subjects. • Prednisone and prednisolone undergo interconversion in liver. On average, the bioavailability of prednisolone after oral prednisone is approximately 80

Background: Ursolic acid is a triterpenoid compound found in natural plants that exhibits antiproliferative effects in various cancer cells. Our study is the first to demonstrate the strong inhibitory effects of ursolic acid on the proliferation of cutaneous T-cell lymphoma (CTCL) cells. We aimed to further investigate the underlying mechanism of the proliferation inhibition induced by ursolic acid in CTCL cells using transcriptome sequencing. Methods: Cell counting kit-8 assays were used to observe the effects of six traditional medicine monomers on the proliferation of CTCL cells. Transcriptome sequencing was used to identify differentially expressed genes after ursolic acid treatment. Bioinformatics analysis was performed to determine the potential mechanism. Real-time quantitative PCR and western blotting analyses were performed to confirm the sequencing results and verify the possible mechanisms of ursolic acid-mediated proliferation inhibition in CTCL cells. Results: Ursolic acid exhibited the strongest inhibitory effect on the proliferation of CTCL cells among the six traditional medicine monomers. Transcriptome sequencing analysis showed that 2,466 genes were significantly altered. Combined with Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis and protein-protein interaction network analysis, the interaction of various pathways and signaling molecules, such as tumor necrosis factor-alpha, NLR family pyrin domain containing 1, c-Jun N-terminal kinase, and melanoma differentiation-associated gene 5, accounted for the anti-tumor effects of ursolic acid in CTCL cells. Conclusion: Ursolic acid significantly inhibited the proliferation of CTCL cells, and our study laid a theoretical foundation for the future treatment of CTCL using ursolic acid.

Background EMLA cream is a local anesthetic. The pharmacokinetics and dermal effects of a topical anesthetic formulation has not been evaluated in healthy Chinese volunteers. Materials and methods The Pharmacokinetics of the lidocaine/prilocaine test (T) or reference (R, EMLA) cream were evaluated in a fasting, single-dose, two-period crossover bioequivalent study conducted in 40 healthy Chinese volunteers. Meanwhile, the dermal effects including blanching, erythema, temperature sensation, edema, and skin rash were also evaluated during the study. Results After applied 15 g of the cream for 4 h to a 100 cm 2 area under plastic occlusive film on the skin of the thigh of healthy volunteers, the results of the pharmacokinetic study showed that the active components absorbed in skin from topical products was relatively low compared with most system absorption drugs. After the removal of the residual anesthetic cream, there was a vascular biphasic response with initial transient blanching which reaches a peak at 4.5 h and later more persisting period erythema. The change of temperature sensory sensitivity reached the peak value at 4.5-6 h.There was no statistically significant difference of the changes after application the lidocaine/prilocaine T or R cream in subjects. In general, the lidocaine/prilocaine T or R cream was well tolerated. Conclusion The method described a model for investigations of pharmacokinetics and pharmacodynamics of topical lidocaine/prilocaine cream. Except the plasma drug level indicator, these pharmacodynamics data should also be evaluated in the anesthetic transdermal pharmacokinetics study. Clinical Trial Registration CTR20211544; registered in http://www.chinadrugtrials.org.cn/ at September 2021.

新型冠状病毒肺炎的发生,给我国各行业都造成了巨大的影响,对临床试验的顺利开展也带来了很多的困难.目前来看,长期抗疫已经不可避免,疫情期间开展临床试验已经成为常态.临床试验中,应该将保护受试者的安全放在首位.本文介绍中国医学科学院皮肤病医院Ⅰ期临床在2020年5月至2020年12月开展的5个临床试验项目,通过试验前期、筛选期、试验期、清洗期、随访期采取的一系列措施,保障受试者的安全,确保临床试验顺利地进行,从而确保试验数据和结果的可靠性、完整性.

目的 研究非那雄胺在中国健康志愿者使用中的安全性,为临床合理用药提供参考.方法 通过2项单次口服5 mg非那雄胺受试制剂和参比制剂的随机、双交叉、2周期的生物等效性研究,共103名中国健康男性志愿者完成了空腹和高脂餐后试验,监测并记录实验室检查参数、生命体征和不良事件.结果 2项试验中,非那雄胺均耐受良好,没有发生严重不良反应.实验室检查异常的不良事件中,血清胆红素水平升高出现的频次最多,最长在10 d内恢复至正常.结论 非那雄胺是一种有效的、选择性的UGT1A4竞争性抑制剂,在血清胆红素的代谢中起关键作用.非那雄胺可能导致血清胆红素升高,建议临床用药时应注意与非那雄胺相关的血清胆红素升高风险.

Objective:To evaluate the inhibitory effect of a retinoid derivative ECPIRM on proliferation of a cutaneous T-cell lymphoma (CTCL) cell line HH, and to explore its potential mechanisms.Methods:Cultured HH cells were treated with ECPIRM at different concentrations of 0 (control group) , 5, 10 and 20 μmol/L separately for 72 hours, cell counting kit-8 (CCK8) assay was performed to evaluate the effect of ECPIRM on the proliferative activity of HH cells, and flow cytometry to investigate the effect of ECPIRM on apoptosis of HH cells. Some HH cells were treated with 10 μmol/L ECPIRM for 72 hours, transcriptome sequencing was performed to investigate gene expression changes triggered by ECPIRM in HH cells, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and gene ontology (GO) enrichment analysis were then performed to analyze differentially expressed genes in HH cells induced by ECPIRM. Reverse transcription-qPCR was subsequently conducted to verify changes in key gene expression in related pathways. Intergroup differences were analyzed by using one-way analysis of variance, and least significant difference (LSD) - t test was used for multiple comparisons. Results:CCK8 assay showed that the 50% inhibitory concentration (IC50) of ECPIRM on HH cells was 4.91 ± 2.48 μmol/L, the viability of HH cells significantly differed among the control group, and 5-, 10-and 20-μmol/L ECPIRM groups (100.00% ± 2.87%, 49.58% ± 4.53%, 48.36% ± 2.88%, 31.44% ± 2.46%, respectively, F=162.86, P < 0.001) , and was significantly lower in the 5-, 10-and 20-μmol/L ECPIRM groups than in the control group ( t=15.36, 15.73, 20.89, respectively, all P < 0.001) . Flow cytometry showed that there was a significant difference in the apoptosis rate among the 4 groups (11.51% ± 1.84%, 23.83% ± 5.72%, 36.19% ± 8.33%, 49.75% ± 4.10%, respectively, F=17.62, P < 0.001) , and the 10-and 20-μmol/L groups showed significantly increased apoptosis rates compared with the control group ( t=4.46, 6.92 respectively, both P < 0.01) . Transcriptomics analysis revealed that the inhibitory effect of ECPIRM on the cellular proliferative activity may be related to the metabolic regulation of steroids. As reverse transcription-qPCR revealed, the 10-μmol/L ECPIRM group showed significantly decreased mRNA expression of L-amino acid oxidase (IL4I1) , acetyl-coenzyme A acetyltransferase 2 (ACAT2) , 3-hydroxy-3-methylglutaryl-coenzyme A synthase 1 (HMGCS1) , mevalonate diphosphate decarboxylase (MVD) , 3-β-hydroxysteroid-8,7-isomerase (EBP) , very low-density lipoprotein receptor (VLDLR) , 3-hydroxy 3-methylglutaryl-CoA reductase (HMGCR) compared with the control group (all P < 0.05) . Conclusion:The retinoid derivative ECPIRM exerted marked anti-proliferative and apoptosis-inducing effects on HH cells, which may be related to the decreased expression of key genes involved in steroid metabolism.

目的 研究奥美拉唑碳酸氢钠干混悬剂在健康人体的药代动力学和相对生物利用度,并以原研奥美拉唑碳酸氢钠干混悬剂为参比制剂,进行生物等效性评价.方法 用单中心、随机、两周期、两交叉、自身对照试验设计,分别入组40例受试者,Ⅰ组交叉口服受试制剂或参比制剂奥美拉唑碳酸氢钠干混悬剂20 mg,Ⅱ组交叉口服受试制剂或参比制剂奥美拉唑干混悬剂40 mg.用LC-MS/MS法测定血浆中奥美拉唑浓度,用WinNonlin 8.0计算药代动力学参数,并进行两种制剂的生物等效性评价.结果 受试者给予受试制剂及参比制剂奥美拉唑碳酸氢钠干混悬剂20 mg后Cmax分别为(869.85±366.05)和(858.38±370.23)ng·mL-1,AUC0-t分别为(1006.33±939.25)和(1022.64±1010.28)h·ng·mL-1.Cmax和AUC0-t的90％置信区间分别为92.93％ ～112.62％ 和95.50％～102.90％.受试者给予受试制剂及参比制剂奥美拉唑碳酸氢钠干混悬剂40 mg后Cmax分别为(2276.00±787.45)和(2162.92±793.21)ng·mL-1,AUC0-t分别为(3937.53±3336.61)和(3929.18±3034.03)h·ng·mL-1.Cmax和AUC0-t的90％置信区间分别为96.41％～117.74％和95.13％～103.49％.药代动力学参数个体间变异均超过25％.结论 受试制剂与参比制剂奥美拉唑碳酸氢钠干混悬剂20 mg和40 mg的药代动力学参数分别在80.00％ ～125.00％等效区间内,表明在中国健康受试者中具有生物等效性.

利伐沙班为临床上常用的抗凝药物,查阅文献,其不良反应未见有白细胞减少.本院开展的一项利伐沙班片在中国成年健康受试者中的一项生物等效性研究中,出现4例不同程度的白细胞减少(空腹受试者A,女性,29岁.餐后受试者B,男,22岁;C,女,29岁;D,女,23岁),并且在停药后白细胞水平恢复正常.故在临床使用利伐沙班时,加强对白细胞的监测.