Multiorgan dysfunction syndrome due to high-dose cantharidin poisoning:A case report

BACKGROUND This report delves into the diagnostic and therapeutic journey undertaken by a patient with high-dose cantharidin poisoning and multiorgan dysfunction syndrome(MODS).Particular emphasis is placed on the comprehensive elucidation of the clinical manifestations of high-dose cantharidin poisoning,the intricate path to diagnosis,and the exploration of potential underlying mechanisms.CASE SUMMARY A patient taking 10 g of cantharidin powder orally subsequently developed MODS.The patient was treated with supportive care,fluid hydration and antibiotics,and hemoperfusion and hemofiltration therapy for 24 h and successfully recovered 8 d after hospital admission.Cantharidin poisoning can cause lifethreatening MODS and is rare clinically.This case underscores the challenge in diagnosis and highlights the need for early clinical differentiation to facilitate accurate assessment and prompt intervention.CONCLUSION This article has reported and analyzed the clinical data,diagnosis,treatment,and prognosis of a case of high-dose cantharidin poisoning resulting in MODS and reviewed the relevant literature to improve the clinical understanding of this rare condition.

Protective effect of glycyrrhetinic acid against cantharidin-induced hepatotoxicity through reducing oxidative stress in mice

Background:Cantharidin(CTD)is a commonly used natural product with anticancer properties;however,it has significant adverse effects,particularly hepatotoxicity.Glycyrrhetinic acid(GA),the active component of licorice,shows potential hepatoprotective effects.The protective effects and mechanism of GA against CTD-induced hepatotoxicity are still unclear.Objective:This study aims to elucidate the effect and mechanism of GA on CTD-induced hepatotoxicity in mice experiments.Methods:Construction of CTD-induced hepatotoxicity models and oral gavage GA intervention for 14 d.The liver index,ALT,AST and LDH levels in the serum of the mice were examined;HE staining was performed to observe pathological changes in the liver.The MDA level and SOD activities in liver tissue were tested.Western blot was conducted to determine Keap1/Nrf2 signaling pathway-related protein expression.Results:The results showed that GA significantly reduced the levels of ALT,AST,and LDH in the serum,which were increased by CTD.Additionally,it also exerted a substantial inhibitory effect on the reduction of SOD activity and the elevation of malondialdehyde content in liver tissue.Notably,the phenomena of nuclear swelling,necrosis,and inflammatory infiltration of liver tissue were significantly attenuated following oral administration of GA in mice.Subsequent research has demonstrated that GA effectively suppressed the CTD-triggered upregulation of Keap1 while increasing the CTD-induced downregulation of Nrf2,HO-1,and NQO1.Conclusion:These findings suggested that GA may protect against CTD-induced hepatotoxicity in mice by exerting antioxidative stress through the Keap1/Nrf2 signaling pathway.

1,2-Cyclic Monoacyl-rac-Glycerothio-phosphates of Cantharidin Analogues

A series of 1,2-cyclic monoacyl-rac-glycerothiophosphates of cantharidin and its analogues were synthesized in a one-pot procedure in overall yields of 44 similar to 55.5% by means of hexaethylphosphorus triamide as phosphorylating reagent.

Inhibitory Effect of Cantharidin on Proliferation of A549 Cells

Objective： To study the inhibition of Cantharidin against the proliferation of human lung cancer A549 cells and its mechanism. Methods： MTT assay was employed to determine the inhibition of Cantharidin against proliferation of A549 cells and flow Cytometry was applied to analyze A549 cell cycle and the effect of Cantharidin on cell cycle. Results： Cantharidin showed inhibition against the proliferation of A549 cells, and the inhibition was mediated by blocking A549 cell cycle at G2/M phase significantly. Conclusion： Cantharidin exhibits inhibition against the proliferation of human lung cancer A549 cells.

Cantharidin suppresses HCT116 colorectal carcinoma cell proliferation and migration by changing the cytoskeleton structure

Background:Cantharidin (CTD),a natural toxin produced from Chinese blister beetles,has extensive anti-tumor activity.The present study investigated the effect of CTD on a human colon cancer cell line to elucidate potential new insights regarding the mechanism(s) through which CTD exerts its anti-tumor effects.Materials and methods:The inhibitory effect of CTD on human colon cancer HCT116 cells was evaluated using the IncuCyte ZOOMTM analyzer.Apoptotic cells were detected by Annexin V-FITC/PI assay and cell cycle was evaluated with flow cytometry following propidium iodide staining.Alterations in F-actin microfilaments were analyzed by FITC-phalloidin staining and morphological changes were evaluated with a laser scanning confocal microscope.Cell migration assay was carried out to investigate the effects of CTD on migration of HCT116 cells in vitro.Results:CTD exhibited a significant growth inhibitory effect on HCT116 cells accompanied by an increase in G2/M phase cells,without a significant effect on apoptosis.CTD-treated cells also exhibited a dramatic collapse in their microfilament network and a significant reduction in cell adhesion.Conclusion:CTD inhibits growth by increasing G2/M phase cells and decreasing S phase cells,revealing that CTD exerts a significant growth inhibitory effect primarily through an inhibition of cell cycle progression (a cytostatic effect).Moreover,a negative effect on cell migration may also constitute a contributing factor to its anti-tumor potential.These findings suggest the potential use for developing CTD as a novel anti-cancer therapy that targets metastasis Giving full play to CTD may inhibit tumor transfer.

Analysis of the metabolic mechanism in Cantharidin-induced hepatotoxicity in LO2 cells using lipidomics analysis

Background:Cantharidin is a major active compound from Banmao(Mylabris).Cantharidin has obvious anticancer activity.However,its clinical application is limited due to serious hepatotoxicity.Methods:To evaluate the toxicity of human liver LO2 cells exposed to cantharidin by lipidomics.After exposing LO2 cells to different doses of cantharidin,the metabolites in LO2 cells were analyzed by nontargeted lipidomics based on liquid chromatography-mass spectrometry.Partial least-squares discriminant analysis and orthogonal partial least-squares discriminant analysis were used to screen differentially expressed metabolites,and then the main metabolic pathways were analyzed.Results:Pattern recognition analysis showed that the lipid metabolite profiles were changed significantly after cantharidin treatment,and 39 differential lipid metabolites were found.Additional analysis showed that these metabolites could mainly involve the metabolic pathways of triglyceride and acylcarnitine for cantharidin toxicity to LO2 cells.Conclusion:Cantharidin has obvious toxic effects on LO2 cells from the perspective of lipid metabolism.Moreover,the LO2 cytotoxicity induced by cantharidin is mainly related to the disorder of triglyceride and acylcarnitine metabolism.It can provide a scientific basis for cantharidin-induced hepatotoxicity.

斑蝥酸钠维生素B_(6)联合化疗药物胸腔内热灌注治疗肺癌合并恶性胸腔积液的疗效和安全性

目的观察斑蝥酸钠维生素B_(6)联合化疗药物胸腔内热灌注治疗肺癌合并恶性胸腔积液的疗效和安全性。方法选取2018—2022年扬中市人民医院收治的肺癌合并恶性胸腔积液患者130例,按照随机抽签法分为A组与B组,各65例。所有患者将胸腔积液完全排出后,A组经导管注入注射用顺铂、地塞米松磷酸钠注射液、注射用人白介素-2胸腔内热灌注,B组在A组基础上加用斑蝥酸钠维生素B_(6)注射液胸腔内热灌注。比较2组临床疗效,KPS评分改善分级,治疗前后肿瘤标志物[癌胚抗原(CEA)、细胞角蛋白19片段抗原21-1(CYFRA21-1)和神经元特异性烯醇化酶(NSE)],不良反应。结果B组客观缓解率高于A组(82.67%vs.50.67%,χ^(2)=17.280,P<0.001)。B组KPS评分改善分级优于A组(u=2.053,P=0.040)。治疗后,2组血清CEA、CYFRA21-1、NSE水平低于治疗前,且B组低于A组(P<0.01)。B组与A组不良反应总发生率比较,差异无统计学意义(34.67%vs.29.33%,χ^(2)=0.490,P=0.484)。结论斑蝥酸钠维生素B_(6)联合化疗药物胸腔内热灌注治疗肺癌合并恶性胸腔积液可提高疗效、改善患者功能状态,抑制肿瘤标志物表达,延缓病情进展,且未提高不良反应发生率。

斑蝥酸钠维生素B_(6)注射液联合顺铂治疗恶性胸腔积液的效果观察

目的:观察斑蝥酸钠维生素B_(6)注射液联合顺铂治疗恶性胸腔积液的效果。方法:选取2022年1月—2023年4月江西省胸科医院收治的60例恶性胸腔积液患者,用随机数字表法分为对照组和治疗组,各30例。对照组采用单纯顺铂胸腔灌注,治疗组采用顺铂联合斑蝥酸钠维生素B_(6)注射液胸腔灌注。比较两组近期疗效、不良反应、肿瘤标志物及血清T细胞亚群。结果:治疗组完全缓解率和总有效率均高于对照组,差异均有统计学意义(P<0.05)。治疗组不良反应总发生率低于对照组,差异有统计学意义(P<0.05)。治疗后1个月,治疗组CEA、CA125及CA199均低于对照组,差异均有统计学意义(P<0.05)。治疗后1个月,治疗组CD4^(+)T细胞、CD8^(+)T细胞及CD4^(+)/CD8^(+)均高于对照组,差异均有统计学意义(P<0.05)。结论:对恶性胸腔积液患者,斑蝥酸钠维生素B_(6)与顺铂联合胸腔灌注,近期疗效较佳,加强抗癌抑癌效应,能有效减少不良反应,机体免疫力可受到保护并有一定程度的提升。

Physicochemical Properties and Gastric Mucosa Irritation of Cantharidin-hydroxypropyl-β-cyclodextrin Inclusion Complex

Objective To increase the solubility and relieve the mucous irritation of cantharidin (CA) by preparing cantharidin-hydroxypropyl-β-cyclodextrin (CA/HP-β-CD) inclusion complex. Methods The inclusion complex was prepared by co-evaporation method and characterized by differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and nuclear magnetic resonance (NMR). Results The disappearance of CA as well as the shift of exothermic peaks shown in DSC results indicated the complexation phenomenon. XRD results showed that the crystalline CA pattern had disappeared, and in NMR results, H-5 shifted from δ 3.731 to 3.695 after complexation and H-2 shifted from δ 3.626 to 3.598, which suggested that part of the drug had entered the HP-β-CD cavity to form an inclusion complex. The solubility increased 10.3 times after complexation and the mucous irritation of CA was relieved remarkably. Conclusion Through complexation with HP-β-CD, the solubility and dissolution rate of CA are improved significantly, and the irritation of musous is relieved.

枯草杆菌二联活菌颗粒联合斑蝥酸钠维生素B_(6)辅助治疗在慢性阻塞性肺疾病合并非小细胞肺癌中的效果研究

目的探讨枯草杆菌二联活菌颗粒联合斑蝥酸钠维生素B_(6)辅助治疗在慢性阻塞性肺疾病(COPD)合并非小细胞肺癌(NSCLC)中的效果。方法选取2020年1月—2022年10月收治的COPD合并NSCLC 60例,采用随机数字表法分为观察组和对照组各30例。2组均给予化疗联合免疫治疗,在此基础上对照组给予斑蝥酸钠维生素B_(6)治疗,观察组给予枯草杆菌二联活菌颗粒联合斑蝥酸钠维生素B_(6)治疗,2组均持续治疗4个周期。统计2组治疗4个周期后总缓解率及治疗前、治疗2个周期、治疗4个周期肿瘤因子[癌胚抗原(CEA)、癌抗原125(CA125)、血管内皮生长因子(VEGF)、缺氧诱导因子(HIF-1α)]、免疫功能指标(CD3+、CD4+、CD4+/CD8+)、肠道微生态指标(肠道菌群丰富度、多样性指数)、治疗期间毒副反应、治疗后1年生存率。结果2组总缓解率比较差异无统计学意义(P>0.05)。治疗后2组CEA、CA125、VEGF、HIF-1α呈下降趋势,CD3+、CD4+、CD4+/CD8+呈升高趋势,差异有统计学意义(P<0.05)。治疗后2组肠道菌群丰富度、多样性指数呈升高趋势,且观察组高于对照组(P<0.05)。观察组胃肠道反应发生率为16.67%(5/30)低于对照组的46.67%(14/30)(P<0.05)。2组治疗后1年生存率比较差异无统计学意义(P>0.05)。结论枯草杆菌二联活菌颗粒联合斑蝥酸钠维生素B_(6)辅助治疗能有效纠正COPD合并NSCLC患者化疗及免疫治疗后肠道菌群紊乱,改善机体免疫应答,抑制肿瘤因子表达,减少毒副反应的发生。

斑螯酸钠维生素B_(6)联合经导管动脉化疗栓塞术和冷循环微波消融治疗肝癌的效果分析

目的探讨斑螯酸钠维生素B_(6)联合经导管动脉化疗栓塞术(TACE)及冷循环微波消融治疗肝癌的临床疗效。方法选取2019年6月至2020年6月本院收治的62例中晚期原发性肝癌患者作为研究对象,根据治疗方法不同分为实验组与对照组,每组31例。对照组给予TACE治疗,实验组给予斑螯酸钠维生素B6联合TACE治疗,比较两组治疗前后生长因子水平、临床疗效及不良反应发生率。结果治疗后,两组碱性成纤维细胞生长因子(bFGF),血管内皮生长因子(VEGF)水平均低于治疗前,且实验组低于对照组,差异有统计学意义(P<0.05)。实验组治疗总有效率为51.61%,高于对照组的35.48%,差异有统计学意义(P<0.05)。实验组不良反应发生率为16.13%,低于对照组的38.71%,差异有统计学意义(P<0.05)。结论斑螯酸钠维生素B6联合TACE及冷循环微波消融治疗肝癌患者效果显著,可降低细胞生长因子水平和不良反应发生率,值得临床推广应用。

斑蝥素固体脂质纳米粒的制备及促肝癌细胞凋亡的研究

目的制备斑蝥素固体脂质纳米粒,并对其进行质量评价及体内外抗肝癌研究。方法采用薄膜超声分散法制备斑蝥素固体脂质纳米粒,以粒径、PDI(Polydispersity Index)、Zeta电位和包封率等为指标,对制备工艺进行优化,通过透射电镜观察纳米粒的形态,并考察其体外释放度,以荧光实验考察肝癌细胞摄取固体脂质纳米粒,以CCK8法研究固体脂质纳米粒使斑蝥素增效减毒的作用、以流式细胞术研究斑蝥素固体脂质纳米粒促细胞凋亡及阻滞细胞周期的情况,以体内裸鼠实验验证斑蝥素固体脂质纳米粒的药效。结果斑蝥素固体脂质纳米粒呈粒径大小均一,形状规整的类球实体形,具有较好的稳定性和良好的药物缓释作用,细胞摄取实验结果显示与游离斑蝥素相比,固体脂质纳米粒更能有效递送药物到细胞。细胞毒性实验结果显示CTD-SLN(cantharidin solid lipid nanoparticles)和CTD(cantharidin)对HepG2细胞均具有显著浓度依赖性的毒作用,且CTD-SLN能够起到增效减毒的作用。流式细胞术的结果发现CTD-SLN能够促进细胞凋亡且使细胞停滞在S期。结论制备得到的斑蝥素固体脂质纳米粒能增强药物促肝肿瘤细胞凋亡效果,可用于进一步研究。

复方斑蝥胶囊联合持续热灌注化疗对进展期胆管癌的疗效研究

目的探讨复方斑蝥胶囊联合持续热灌注化疗(CHPPC)用于进展期胆管癌的治疗效果。方法选取进展期胆管癌患者100例,采用随机对照表法分为观察组与对照组,各50例。对照组于胆管癌姑息切除术后给予CHPPC治疗,观察组采用复方斑蝥胶囊联合CHPPC治疗,共治疗6个疗程。评价2组治疗后临床疗效,观察2组治疗前后KPS评分变化,全自动生化分析仪检测患者肝功能指标(TB、AST、ALT、γ-GT)水平变化,ELISA实验检测患者血清中肿瘤标志物(CEA、CA199、CA125)水平变化,记录患者不良反应发生情况。结果2组治疗前各指标差异均无统计学意义(P>0.05),治疗后,观察组临床有效率较对照组显著提高,2组TB、AST、ALT、γ-GT肝功能及CEA、CA19-9、CA125肿瘤标志物水平均明显下降(P<0.05),生活质量较治疗前明显改善(P<0.05);观察组TB、AST、ALT、γ-GT及CEA、CA19-9、CA125水平较对照组均显著降低(P<0.05),生活质量改善率较对照组明显提高(P<0.05),不良反应发生率明显低于对照组(P<0.05)。结论复方斑蝥胶囊联合CHPPC治疗能够进一步改善进展期胆管癌患者的临床症状,改善患者肝功能和生活质量,疗效更好,能够减轻不良反应,安全性较好。

复方斑蝥胶囊联合培美曲塞和铂类化疗对晚期肺腺癌患者疗效的影响

目的:探究复方斑蝥胶囊联合培美曲塞+铂类化疗对晚期肺腺癌患者疗效的影响。方法:选取2017年1月至2021年12月德驭医疗马鞍山总医院收治的晚期肺腺癌患者80例作为研究对象,随机分为观察组和对照组,每组40例。对照组接受培美曲塞+铂类药物一线治疗,观察组在对照组基础上加用复方斑蝥胶囊。比较2组近期疗效、肿瘤标志物水平、免疫功能、不良反应发生情况和无进展生存期(PFS)。结果:观察组客观有效率(ORR)、疾病控制率(DCR)均高于对照组(均P<0.05)。治疗后,观察组癌胚抗原(CEA)、组织多肽特异性抗原(TPS)、糖类抗原153(CA153)水平低于对照组,CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平高于对照组(均P<0.05)。观察组血小板下降、白细胞下降、胃肠道反应和骨髓抑制发生率低于对照组(均P<0.05)。观察组中位PFS长于对照组(P<0.05)。结论:复方斑蝥胶囊可提高培美曲塞+铂类药物治疗晚期肺腺癌的近期疗效,在降低肿瘤标志物水平的同时,改善患者免疫功能,减少不良反应发生。

气相色谱-质谱法测定化妆品中斑蝥素和氮芥

建立气相色谱-质谱法同时测定化妆品中斑蝥素和氮芥的含量。以色谱纯三氯甲烷为溶剂提取化妆品中的斑蝥素和氮芥两种组分,用气相色谱-质谱(GC-MS)法进行分析,各目标组分均能有效分离,且色谱峰形良好。斑蝥素和氮芥在质量浓度0.5~10μg/mL范围内线性良好,线性相关系数均为0.998,平均加标回收率分别为102.6%和115.7%。测定结果的相对标准偏差分别为1.2%和2.1%(n=6)。该方法适用于化妆品中斑蝥素和氮芥两种禁用组分同时测定。

急性斑蝥中毒致口腔黏膜病变及流产1例及文献复习

目的加深医护人员对急性斑蝥中毒的临床诊治的理解。方法回顾性分析1例孕早期急性斑蝥中毒患者的临床资料,分析其临床特点、检查及诊断方法、治疗策略、发病机制及预后转归,并进行文献复习。结果本例患者以口咽及消化系统黏膜病变损伤表现发病,实验室检查见感染、肝肾功能损伤及内环境代谢紊乱,经过早期多学科协作,对患者综合干预,行利尿解毒、保护黏膜及纠正机体内环境代谢紊乱,患者治疗预后良好,无继发及余留并发症。结论急性斑蝥中毒是一种罕见的中毒性疾病,应根据患者的具体情况进行个体化、对症治疗,安全地解毒后使用黏膜保护剂能有效减轻患者主观症状,联合多科诊疗用药可减少重要脏器及功能继发损害,提高其预后及治愈率。

复方桐叶烧伤油治疗斑蝥酸钠维生素B6所致静脉炎60例

目的 分析复方桐叶烧伤油在斑蝥酸钠维生素B6所致静脉炎患者中的治疗效果。方法 选取江西省肿瘤医院2020年4月至2022年4月收治的斑蝥酸钠维生素B6所致静脉炎患者120例,按随机数字表法划分成对照组(60例)、观察组(60例)。对照组给予多磺酸黏多糖乳膏,观察组予以复方桐叶烧伤油外擦,连续治疗1周。对比两组临床疗效、症状改善情况、舒适度、不良反应。结果 观察组治疗总有效率为95.00%(57/60),高于对照组的83.33%(50/60),皮肤灼热消失时间、局部红肿消失时间、疼痛消失时间、血管条索状改变消失时间均短于对照组,简化舒适状况量表内生理维度评分、心理维度评分、精神维度评分、社会文化和环境维度评分均高于对照组,差异有统计学意义(P<0.05);两组不良反应差异无统计学意义(P>0.05)。结论 复方桐叶烧伤油在斑蝥酸钠维生素B6所致静脉炎患者治疗中效果显著,可加快其症状消退,提高舒适度,且安全性较高。

复方斑蝥胶囊联合辅助化疗对结直肠癌术后患者复发转移的预防效果及安全性

目的探讨复方斑蝥胶囊联合辅助化疗对结直肠癌术后患者复发转移的预防效果及安全性。方法选取医院2019年8月至2021年8月期间收治的结直肠癌患者78例为研究对象,随机将其分为2组,各39例。对照组术后给予辅助化疗,在此基础上观察组给予复方斑蝥胶囊治疗。比较两组术后复发转移、身体功能状况、生活质量、安全性。结果观察组转移复发发生率低于对照组,差异有统计学意义(P<0.05);治疗后两组KPS评分提高,且观察组高于对照组,差异有统计学意义(P<0.05);治疗后两组生理领域、心理领域、独立性领域、环境领域评分提高,且观察组高于对照组,差异有统计学意义(P<0.05);观察组骨髓异常、白细胞下降、胃肠道反应、血小板下降、乏力发生率低于对照组,差异有统计学意义(P<0.05)。结论复方斑蝥胶囊联合辅助化疗可降低结直肠癌术后患者复发转移率,改善躯体功能状况,提高生活质量,且安全性较高。

斑蝥素经PI3K/Akt/PKC通路对血小板功能的调控作用

目的 探讨斑蝥素(Cantharidin,CTD)对血小板功能的影响和抗血小板聚集的作用机制。方法 采集健康志愿者静脉血,提取洗涤血小板,聚集仪检测CTD(2.5、5、10μmol·L^(-1))对胶原、凝血酶、ADP和佛波酯(Phorbol-12-myristate-13-acetate,PMA,PKC激动剂)诱导的血小板聚集,和对ATP释放的影响。荧光显微镜拍照观察CTD对纤维蛋白原表面的血小板扩展功能和对血小板斑块回缩的影响。检测CTD联用740Y-P(PI3K特异性激动剂)对胶原诱导血小板的聚集率,Western blot检测PI3K蛋白磷酸化水平。小鼠腹腔注射CTD(0.35、0.7 mg·kg^(-1))和阿司匹林(30 mg·kg^(-1)),观察胶原诱导各组离体血小板聚集率,检测PI3K、Akt和PKC蛋白磷酸化水平,检测凝血指标凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)和小鼠断尾流血时间。结果 CTD抑制胶原、凝血酶和PMA诱导的血小板聚集和抑制ATP释放,对ADP诱导的血小板聚集无影响,CTD抑制血小板扩展和斑块回缩,740Y-P处理能够减弱CTD对胶原诱导的血小板聚集的抑制作用。CTD抑制离体血小板聚集功能和PI3K、Akt和PKC磷酸化水平,延长APTT和小鼠尾巴出血时间。结论 CTD抑制血小板聚集、释放、扩展、斑块回缩和影响止血功能,其机制与调控PI3K、Akt和PKC蛋白磷酸化水平有关。

斑蝥酸钠对卡培他滨在大鼠体内药动学行为的影响

目的考察斑蝥酸钠对卡培他滨在大鼠体内药动学行为的影响。方法将大鼠随机分为2个对照组和2个实验组,每组6只。2个对照组大鼠腹腔注射生理盐水,2个实验组腹腔注射斑蝥酸钠注射液0.5 mL/kg,连续给药7 d;第8天给药后,对照1组和实验1组大鼠灌胃卡培他滨5 mg/kg,对照2组和实验2组大鼠静脉注射卡培他滨5 mg/kg。于给药后不同时间点采集血样。血样经乙酸乙酯萃取后,以甲苯磺丁脲为内标,采用超高效液相色谱-串联质谱法测定大鼠血浆中卡培他滨的浓度,采用DAS 2.0软件计算主要药动学参数。结果与对照1组比较,实验1组无穷大时间内的平均滞留时间(MRT_(0-∞))、峰浓度(c_(max))、30 h内的药-时曲线下面积(AUC_(0-30 h))、AUC_(0-∞)和生物利用度(F)均显著升高,表观清除率(CLz/F)显著降低(P<0.01);与对照2组比较,实验2组的半衰期(t_(1/2))、MRT_(0-30 h)、MRT_(0-∞)、AUC_(0-30 h)、AUC_(0-∞)均显著升高(P<0.01)。结论斑蝥酸钠能增加卡培他滨在大鼠体内的血浆暴露量,提高口服生物利用度,延长平均滞留时间,降低清除率。