吡喹酮制剂的发展和应用

吡喹酮是临床有效治疗血吸虫病的首选药物, 然而其生物利用度低、 剂型单一、 对童虫作用不明显等缺点, 限制了其发挥最大效用。本文针对吡喹酮性质及药代动力学特点, 并结合现有吡喹酮新型制剂的研究进展做一综述, 为充分发挥吡喹酮的抗血吸虫作用以及吡喹酮新制剂的研究开发提供参考及借鉴。     

不同剂型利福平投药后血药浓度的监测结果分析

目的 分析两种不同剂型利福平投药后血药浓度的监测结果,以指导临床合理用药。方法 选择2016年5月至2017年6月昆明市第三人民医院结核二科收治的活动性肺结核患者130例,按照数字表法随机分为注射组(65例;利褔平采用静脉滴注的方式,0.6g/次,1次/d,用500ml 5%葡萄糖注射液配制)和口服组(65例;利褔平采用口服的方式,0.6g/次,1次/d);利福平最低抑菌浓度(MIC)为0.39~1.56μg/ml,本研究统计达到MIC为0.39μg/ml的患者例数。口服组最终有2例患者因不同时间点血药浓度监测数据存在遗漏,故剔除,本研究最终纳入128例患者,其中注射组65例,口服组63例。两组患者用药第7天后,采集不同时间点的血浆标本,通过超高效液相色谱-串联质谱法(UPLC-MS/MS)检测两组利福平的血药浓度值。结果 注射组利福平最高血药浓度出现在输注后1.5h,中位数(四分位数)[M(Q₁,Q₃)]为0.954(0.210,3.420)μg/ml;口服组最高血药浓度出现在服药后2h,M(Q₁,Q₃)为1.253(0.249,2.501)μg/ml。注射组峰值血药浓度为1.786(0.704,3.591)μg/ml,均值血药浓度为0.688(0.269,1.087)μg/ml,均高于口服组[分别为1.468(0.423,3.748)μg/ml和0.571(0.149,1.894)μg/ml],但差异均无统计学意义(Z值分别为-0.90和-0.02,P值分别为0.366和0.980);注射组谷值血药浓度为0.004(0.001,0.038)μg/ml,低于口服组[0.007(0.001,0.070)μg/ml],差异有统计学意义(Z=-8.74,P=0.000)。注射组总体达到MIC的比率为47.7%(248/520),口服组为49.4%(218/441),差异无统计学意义(χ²=0.29,P=0.591)。结论 患者采用注射和口服利福平的治疗方案,血药浓度值均较低,有超过50%的患者总体时间内并未达到MIC,无法满足利福平推荐的参考范围,可能存在剂量上的不足;应继续加强对利福平血药浓度的监测,规范使用利福平注射液。     

Controlled cyclophotocoagulation

Background: In the past, the main problem of transscleral cyclophotocoagulation was related to the energy dosage of the individual effect. Since the target tissue is not directly observable, no information about the coagulation process was available to the surgeon. High inter- and intraindividual variations of the tissue properties often led to under- or overdosage. Underdosage is therapeutically useless, while overdosage causes the so-called “popeffects” which may induce severe damage to the eye. Solution: A small fraction of the impinging laser radiation passes the ciliary body after multiple scattering, is reflected from the fundus, leaves the eye through the optical media and can be recorded by a photodetector outside the eye. The time dependence of this detector signal directly monitors the change in transmission of the coagulated tissue, because all other parameters influencing the signal are constant in time. Using this information, the surgeon or a computer can interrupt the laser process. Clinical evaluation: In the eyes treated since September 1996, a mean reduction of intraocular pressure was achieved comparable to the values for uncontrolled cyclophotocoagulation reported in the literature. So far, no case of severe complications has been observed. Conclusion: The accuracy and safety of transscleral cyclophotocoagulation are improved by this real-time control procedure. Reduction of risk may allow broader application of the method.      

硫酸吗啡控释片剂量滴定控制癌性疼痛的临床研究

目的：评价硫酸吗啡控释片通过剂量滴定对癌性疼痛的治疗作用。方法;本次研究共收治１４８例中重度癌症疼痛患者,硫酸吗啡控释片的初始剂量一般由１０－３０ｍｇ开始,观察１－２天疼痛无缓解即进行个体剂量滴定,按３０％－５０％剂量逐渐递增,直到能缓解。如经放,化疗后疼痛减轻而需要减量时,按３０％－５０％剂量递减。整个治疗期间随时进行剂量滴定,一直观察到用药终止。     

Drug and metabolite concentrations combined in predicting steady-state concentrations from test doses

The first day test dose versus steady-state relationship for predicting drug doses was evaluated for the situation where metabolites are produced. An organ clearance model incorporated into a digital computer program simulated drug and metabolite disposition. When the terminal elimination rate for metabolite was similar to that of its precursor, the drug and metabolite concentrations could be summed for use in test dose predictions as the resulting accumulation ratios were similar. However, if an active metabolite is eliminated more slowly than its precursor, future studies should consider these concentrations separately for predictive purposes. The theoretical results agreed with concentration data obtained from a study of patients who took imipramine.     

高压氧治疗脑卒中的剂量研究

观察２２例脑卒中患者在高压氧治疗不同时期体内自由基代谢物质含量的变化。每天用０．２ＭＰａ高压氧稳压治疗４０ｍｉｎ，连续治疗２０天。结果发现，经高压氧连续治疗１０天，患者血浆ＬＰＯ含量的增加和红细胞ＳＯＤ、ＧＳＨＰｘ活性的下降都不明显（Ｐ＞０．０５），仅红细胞明显降低（Ｐ＜０．０５）；连续治疗２０天后，患者血浆ＬＰＯ含量明显增高，红细胞ＳＯＤ和ＧＳＨＰｘ活性及ＧＳＨ含量显著下降（Ｐ＜０．０５）。建议     

美沙酮维持治疗者服药剂量不足及吗啡尿检阳性与脱失的关系

目的 了解美沙酮维持治疗（MMT）门诊治疗患者的脱失情况,探讨美沙酮剂量<100 mg/d和吗啡尿检阳性与脱失的关系及交互作用。方法 2014年9-11月对广西壮族自治区3个MMT门诊1 031例患者开展问卷调查,收集一般人口学特征、HIV感染、既往吸毒及吗啡尿检等信息。通过单因素和多因素logistic回归分析脱失的相关因素,通过交互作用分析探讨美沙酮剂量<100 mg/d与吗啡尿检阳性与脱失的关系。结果 1 031例MMT患者的脱失率为40.6%（419/1 031）,尿检阳性者和美沙酮剂量<100 mg/d者的脱失率分别是57.6%（99/172）和37.4%（347/929）,高于尿检阴性者（42.3%,363/859）和美沙酮剂量≥100 mg/d者的脱失率（26.5%,27/102）。控制混杂因素后,美沙酮剂量<100 mg/d者比剂量≥100 mg/d者更易于发生脱失（OR=3.05,95%CI：1.84~5.06）,尿检阳性者比阴性者更易于发生脱失（OR=2.25,95%CI：1.59~3.19）。美沙酮剂量<100 mg/d和吗啡尿检阳性存在相加（RERI=256.46,AP=0.87,S=8.05）和相乘（OR=2.45,95%CI：1.71~3.49）交互作用且方向一致。结论 MMT中,美沙酮剂量<100 mg/d及吗啡尿检阳性与脱失呈明显相关。     

姜黄素抗胃癌研究进展

姜黄素（curcumin）是从植物姜黄中提取的多酚类化合物,是姜黄的主要活性成分。姜黄素有显著的药理作用,包括近年来被发现的较强的抑制胃癌扩散的效果。姜黄素抑制胃癌的作用机理主要有抑制肿瘤细胞的扩散和转移、诱导细胞凋亡以及逆转化学药物的耐受性,本文从细胞水平上通过不同的信号通路阐述其作用机理。由于姜黄素具有水溶性差以及口服利用度低的特点,因此临床上通常优化姜黄素的剂型提高疗效。