单剂量肌肉注射甲磺酸齐拉西酮在健康人体的药动学研究

目的:研究单剂量肌肉注射甲磺酸齐拉西酮后药动学。方法:健康受试者10名肌肉注射甲磺酸齐拉西酮注射液20mg后不同时间取静脉血,高效液相色谱法测定其血药浓度,计算药动学参数,数据经3p97程序分析。结果:血药浓度-时间曲线为二室模型。药动学参数Cmax(866.32±482.88)ng/ml,tmax(0.57±0.23)h,t1/2ke(2.17±1.04)h,CL(17.0±9.00)ml/h,AUC0~12(1467.94±644.80)(ng.h)/ml,AUC0~∝(1603.48±722.47)(ng.h)/ml。结论:10名健康受试者肌肉注射甲磺酸齐拉西酮注射液20mg后药动学参数与国外文献报道结果基本一致。     

甲磺酸加替沙星与加替沙星的药物代谢动力学比较

目的甲磺酸加替沙星(GATM)和加替沙星(GAT)是喹诺酮类抗感染药物的新型制剂,对改变酸根的甲磺酸加替沙星在大鼠体内的药物代谢动力学规律和特点进行了考察并和加替沙星进行比较。方法以SD大鼠为研究对象,单剂量口服等克分子剂量(0.0497 mmol.kg-1)GATM和GAT后,采用高效液相色谱法(HPLC)检测血清中GAT的含量,采用3p97程序软件计算二者在大鼠体内的药代动力学参数。结果大鼠单次口服GATM(23.43 mg.kg-1)和GAT(20 mg.kg-1)后,二者的血药浓度经时变化符合一级消除动力学特征,药时曲线拟合为二房室模型,其中GATM的药代动力学参数为:血浆消除半衰期(T12β)9.13 h,药时曲线下面积(AUC)15.05 mg.L-1.h,血药峰浓度(Cm ax)4.41mg.L-1,达峰时间(Tm ax)0.5 h;而GAT的药代参数分别为:T12β10.70 h,AUC 13.84 mg.L-1.h,Cm ax4.25 mg.L-1,Tm ax0.5 h。结论在上述剂量条件下GATM与GAT的吸收(Tm ax、Cm ax、AUC)、分布(V/F)和消除(T12β、CL)参数差异未见显著性,二者的血药浓度经时变化相似,药代动力学规律基本一致。     

高效液相色谱法测定血清中甲磺酸帕珠沙星的浓度

目的:建立人血清中甲磺酸帕珠沙星的高效液相色谱检测方法。方法:采用C18色谱柱(4.6mm×150mm,5μm);柱温:室温;流动相:0.04mol·L-1磷酸-乙腈-三乙胺(87∶13∶0.5,pH3.3);流速:1.0mL·min-1;内标:奥硝唑;检测波长:248nm。结果:甲磺酸帕珠沙星在1.0~15.0mg·L-1范围内线性关系良好(r=0.9998,n=6),平均提取回收率为85.24%,RSD为2.59%,方法回收率为97.47%,RSD为0.76%,日内RSD为4.88%,日间RSD为7.12%。结论:该方法快速、准确、灵敏度高、专一性强,可用于甲磺酸帕珠沙星血清浓度监测和药动学及生物利用度研究。     

甲磺酸伊马替尼治疗手术后复发和/或转移的胃肠道间质瘤的疗效分析

目的:评价甲磺酸伊马替尼治疗无法手术完全切除、术后复发和(或)转移性胃肠间质瘤(GIST)的临床疗效及不良反应。方法:2004年8月～2007年2月间经术后病理证实为GIST,术中无法完全切除病灶或术后复发、转移,失去手术机会,给予甲磺酸伊马替尼治疗400～600mg/d口服的患者21例。结果:21例全部随访,完全缓解(CR)者2例(9.5%),部分缓解(PR)者11例(52.4%),病情稳定(SD)者5例(23.8%),病情进展(PD)3例(14.3%),其中死亡2例(9.5%)。患者获益(CR+PR+SD)率(85.7%),1年、2年生存率分别为100%、83.3%。结论:甲磺酸伊马替尼治疗GIST疗效肯定,不良反应轻,毒性可耐受。     

甲磺酸罗哌卡因复合盐酸奈福泮用于剖宫产术后硬膜外自控镇痛的临床研究

目的 比较剖宫产术后两种硬膜外自控镇痛效果及恶心呕吐、嗜睡、尿潴留发生率.方法 60例剖宫产患者随机分成两组,每组各30例,术毕分别接硬膜外自控镇痛泵.I组:0.15%盐酸布比卡因加曲马多;Ⅱ组:0.179%甲磺酸罗哌卡因加盐酸奈福泮,观察并记录术后48 h内各时点的视觉模拟评分(VAS)和对应时点下肢运动阻滞程度(Bromage评分)及术后恶心呕吐、嗜睡、尿潴留等不良反应发生率.结果 两组术后6、12、24、36 h VAS比较差异无统计学意义(P>0.05);Bro-Inage评分Ⅰ组各时点分别为(2.75±0.49)分、(1.51±0.42)分、(0.92±1.08)分、(0.89±0.12)分,Ⅱ组分别为(1.31±0.57)分、(0.35±0.31)分、(0.08±0.30)分、(0.06±0.28)分,两组比较差异有统计学意作者单位:252601 山东临清,聊城市第二人民医院麻醉科义(P<0.05);恶心呕吐、嗜睡、尿潴留发生率Ⅰ组分别为16.7%、13.3%、50.0%,Ⅱ组分别为6.7%、3.3%、10.0%,两组比较差异有统计学意义(P<0.01).结论 甲磺酸罗哌卡因复合盐酸奈福泮行硬膜外自控镇痛效果确切,在运动功能恢复,降低恶心呕吐、嗜睡、尿潴留发生率方面显示明显优越性.     

Priapism induced by intracavernosal vasoactive intestinal polypeptide and phentolamine mesylate

This is a case of priapism (21 h) following an intracavernosal injection of vasoactive intestinal polypeptide (VIP) 25 mcg with phentolamine mesylate (PM) 1 mg responding to venesection and intracavernosal injection of 1 mg metaraminol.     

Cytogenetic remission with imatinib therapy in hypereosinophilic syndrome with trisomy 8 and resolution of severe cardiac dysfunction

We report a 50-year-old patient with idiopathic hypereosinophilic syndrome with trisomy 8 who experienced a complete and durable hematological and cytogenetic remission with low-dose imatinib therapy. He also had a significant reversal of cardiac dysfunction with a reduction in cardiac hypertrophy, resolution of pericardial effusion and mitral and tricuspid regurgitation. He remained in remission 3 years after therapy.     

Lack of clinical efficacy of imatinib in metastatic melanoma

This two-centre phase-II trial aimed at investigating the efficacy of imatinib in metastasised melanoma patients in correlation to the tumour expression profile of the imatinib targets c-kit and platelet-derived growth factor receptor (PDGF-R). The primary study end point was objective response according to RECIST, secondary end points were safety, overall and progression-free survival. In all, 18 patients with treatment-refractory advanced melanoma received imatinib 800 mg day(-1). In 16 evaluable patients no objective responses could be observed. The median overall survival was 3.9 months, the median time to progression was 1.9 months. Tumour biopsy specimens were obtained from 12 patients prior to imatinib therapy and analysed for c-kit, PDGF-Ralpha and -Rbeta expression by immunohistochemistry. In four cases, cell lines established from these tumour specimens were tested for the antiproliferative effects of imatinib and for functional mutations of genes encoding the imatinib target molecules. The tumour specimens stained positive for CD117/c-kit in nine out of 12 cases (75%), for PDGF-Ralpha in seven out of 12 cases (58%) and for PDGF-Rbeta in eight out of 12 cases (67%). The melanoma cell lines showed a heterogenous expression of the imatinib target molecules without functional mutations in the corresponding amino-acid sequences. In vitro imatinib treatment of the cell lines showed no antiproliferative effect. In conclusion, this study did not reveal an efficacy of imatinib in advanced metastatic melanoma, regardless of the expression pattern of the imatinib target molecules c-kit and PDGF-R.     

Unexpected rapid progression of metastatic adenoid cystic carcinoma during treatment with imatinib mesylate

BACKGROUND: There is a lack of effective treatment for metastatic adenoid cystic carcinoma (ACC), a usually indolent tumor. We studied the efficacy of imatinib mesylate, a potent inhibitor of KIT tyrosine kinase, in patients with KIT-positive metastatic ACC. METHOD: Five patients with lung metastasis were treated in a pilot study with imatinib 400 mg by mouth twice a day. Mutations of c-kit and platelet-derived growth factor receptor (PDGFR)-alpha in tumors from these patients were analyzed. RESULTS: Disease progression was noted in three of five patients during the short treatment periods, ranging from 2 to 3 weeks. Three patients died of disease within 6 months. No detectable mutations were found in c-kit and PDGFR-alpha. CONCLUSION: We observed an unexpected high progression rate of metastatic ACC within short periods during imatinib treatment. Use of imatinib to treat cancers without c-kit or PDGFR-alpha mutation should be approached with caution.