紫杉醇原位凝胶在EAC荷瘤小鼠体内药动学研究

目的:考察紫杉醇原位凝胶制剂PECT/PTX小鼠瘤体内植入后的药动学特点,评价该制剂是否具有控释、缓释作用。方法:对EAC荷瘤小鼠分别进行PECT/PTX瘤体内给药(A组,40 mg·kg^-1),PTX瘤体内给药(B组,40 mg·kg^-1)和PTX腹腔给药(C组,40 mg·kg^-1),给药后于设定的时间点采血,应用HPLC法测定血浆中PTX的含量,DAS 2.1.1药动学分析软件计算主要药动学参数。结果:血浆中A、B、C 3组的C_max分别为(2.23±0.16),(25.25±0.83),(258.38±10.34)mg·L^-1;t_1/2分别为(473.81±195.13),(10.89±0.87),(17.87±6.29)h;AUC_0-t分别为(623.57±23.48),(340.72±2.73),(843.35±25.93)mg·L^-1·h;V_d分别为(17.01±2.24),(1.76±0.13),(1.07±0.25)L·kg^-1;CL分别为(0.024±0.010),(0.105±0.001),(0.040±0.004)L·h^-1·kg^-1。与B组相比,A、C 2组主要药动学参数均具有显著的统计学差异(P<0.01)。结论:PECT/PTX原位凝胶制剂瘤体内给药具有缓慢释放PTX的作用。     

胺碘酮辅助下对照分析依那普利和坎地沙坦治疗阵发性房颤的临床疗效

目的探讨胺碘酮辅助下对照分析依那普利和坎地沙坦治疗阵发性房颤的临床疗效。方法选取在本院接受治疗的阵发性房颤患者共110例,随机将所有患者分为研究1组和研究2组各55例。研究1组采用胺碘酮联合依那普利进行治疗,研究2组采用胺碘酮联合坎地沙坦进行治疗。结果治疗后3、6、9、12及18个月时两组患者的窦性心律维持率比较,差异均无统计学意义（P〉0．05）;两组患者的左心房内径比较,差异均无统计学意义（P〉0．05）。结论采用胺碘酮联合依那普利或坎地沙坦治疗阵发性房颤,均可明显控制患者的左心房内径并有效维持窦性心律,疗效显著,值得推广应用。     

依那普利叶酸片治疗血管性痴呆伴H型高血压的效果分析

目的 探究血管性痴呆（VD）伴H型高血压应用依那普利叶酸片的治疗效果。方法 选取我院2015年4月~2016年4月收治的VD伴H型高血患者64例,随机分为观察组和对照组,每组32例。对照组给予依那普利片治疗,观察组给予依那普利叶酸片治疗,比较两组患者治疗前后血清Hcy、BP水平以及MMSE评分变化情况。结果 两组患者治疗后血清Hcy、BP水平均有所下降,观察组血清Hcy水平为（10.83±1.49）μmol/L,明显低于对照组的（18.42±0.35）μmol/L,差异有统计学意义（P＜0.05）;两组患者治疗后MMSE评分均有所提高,观察组的评分为（20.83±2.49）分,高于对照组的（17.87±2.46）分,差异有统计学意义（P＜0.05）。结论 AD伴H型高血压患者使用依那普利叶酸片的治疗效果明显优于依那普利片,极大改善了患者的血清Hcy水平和血压,患者精神状态较好,具有较高的应用价值。     

依那普利治疗高血压左室肥厚和左室舒张功能

目的：探讨依即普利对高血压左室肥厚与左室舒张功能的治疗作用。方法：对符合ＷＨＯ诊断标准的原发性高血压左室肥厚,服用依那普 治疗,用彩色普勒超声心电图测定治疗前后左室肥厚、左室收缩及舒张功能指标。结果：治疗后室间隔厚度、左室后壁厚度、左室心肌重量均明显减少,舒张早期流速峰值明显增大,房缩期最大流速下降,两比值下降,左室射血分数无变化。结论：依那普利可有效地抑制并逆转左室肥厚,改善左室舒张功能。     

Simultaneous quantification of enalapril and enalaprilat in human plasma by high-performance liquid chromatography–tandem mass spectrometry and its application in a pharmacokinetic study

A rapid, selective and sensitive high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) method was developed to simultaneously determine enalapril and enalaprilat in human plasma. With benazepril as internal standard, sample pretreatment involved in a one-step protein precipitation (PPT) with methanol of 0.2 ml plasma. Analysis was performed on an Ultimate™ XB-C₁₈ column (50 mm × 2.1 mm, i.d., 3 μm) with mobile phase consisting of methanol–water–formic acid (62:38:0.2, v/v/v). The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction-monitoring (MRM) mode via electrospray ionization (ESI) source. Each plasma sample was chromatographed within 2.5 min. The linear calibration curves for enalapril and enalaprilat were both obtained in the concentration range of 0.638–255 ng/ml (r² ≥ 0.99) with the lower limit of quantification (LLOQ) of 0.638 ng/ml. The intra-day precision (R.S.D.) was below 7.2% and inter-day R.S.D. was less than 14%, while accuracy (relative error R.E.) was within ±8.7 and ±5.5%, determined from QC samples for enalapril and enalaprilat which corresponded to requirement of the guidance of FDA. The HPLC–MS/MS method herein described was fully validated and successfully applied to the pharmacokinetic study of enalapril maleate capsules in 20 healthy male volunteers after oral administration.     

依那普利联合不同药物治疗慢性肾小球肾炎疗效分析

目的探讨依那普利联合不同药物治疗慢性肾小球肾炎的治疗效果。方法选择笔者所在医院收治的82例慢性肾小球肾炎患者的临床资料,随机分为观察组和对照组各41例,观察组采用口服依那普利联合静脉滴注灯盏细辛注射液进行治疗;对照组采用口服依那普利联合静脉滴注阿魏酸钠注射液进行治疗。结果观察组的总有效率和显效率均明显高于对照组,差异有统计学意义(P<0.05)。结论依那普利联合灯盏细辛注射液在治疗慢性肾小球肾炎的疗效方面明显优于依那普利联合阿魏酸钠注射液,值得在临床上推广应用。     

硝苯地平控释片与依那普利治疗稳定型心绞痛的临床观察

目的:比较观察硝苯地平控释片与依那普利治疗稳定型心绞痛的临床疗效。方法:将2008年9月-2010年9月,于我院收治的92例稳定型心绞痛患者随机分为硝苯地平控释片组和依那普利组,每组46例,比较观察2组的临床疗效。结果:2组症状改善疗效总有效率和心电图改善疗效总有效率比较,差异无统计学意义(P>0.05)。2组治疗前后心绞痛发作次数、心绞痛持续时间和硝酸甘油消耗量比较,差异均无统计学意义(P>0.05)。硝苯地平控释片组治疗后左心室射血分数(LVEF)水平明显升高,与治疗前比较差异有统计学意义(P<0.05);而依那普利组治疗前、后比较,差异无统计学意义(P>0.05)。依那普利组治疗后LVEF水平明显高于同期硝苯地平控释片组,差异有统计学意义(P<0.05)。结论:硝苯地平控释片与依那普利治疗稳定型心绞痛的临床疗效相当,但依那普利较硝苯地平控释片能够更好的改善左心室收缩功能,为临床治疗稳定型心绞痛提供更多的选择。     

Factors to consider when selecting a nebulizer for a new inhaled drug product development program

Introduction: Nebulizers are a common device choice for use when developing a new drug product, but the range of nebulizer devices available can make it difficult to select the right device. Increasingly, companies are only able to promote a drug with the device that was used during the development program; therefore, choosing the best device at an early stage is important in order to achieve commercial success. Selecting a device that is inappropriate for the intended drug can result in poor drug delivery from the nebulizer to the patient, which would have obvious implications for the development program. As device performance varies, it is important to ensure that the most appropriate device is chosen for the intended drug to ensure optimal drug delivery to the patient population.

Areas covered: In this review, the types of nebulizer devices available are highlighted, and the factors that should be taken into consideration when selecting the most appropriate device for a new drug are discussed. The review is broadly divided into drug, device, patient and trial characteristics.

Expert opinion: Efficient nebulizer devices that combine electronic monitoring capabilities as a form of telehealth are likely to provide superior drug delivery to patients and accurate clinical trial data. Their use in adaptive clinical trials may help to vastly reduce the time and costs associated with achieving drug approval.     

依那普利联合灯盏花素对糖尿病大鼠肾脏保护作用及机制

目的探讨依那普利联合灯盏花素对大鼠糖尿病肾脏保护作用及机制。方法大鼠随机分5组：对照组、糖尿病组、依那普利给药组、灯盏花素给药组及依那普利与灯盏花素联合给药组。8周后观察肾组织病理形态学变化，检测尿白蛋白排泄率（AER）、肾组织尿丙二醛（MDA）含量及肾组织蛋白激酶（PKC）活性；应用Western杂交检测肾组织PKC蛋白表达，免疫组化方法检测肾组织转化生长因子（TGF）β1蛋白表达。结果各给药组均可抑制糖尿病大鼠AER增加及肾组织病理结构损害，联合组优于单独给药组；对肾组织及尿MDA含量增加的抑制作用联合组也优于单给药组；各给药组均可抑制肾组织PKC活性与表达，以联合组最明显；糖尿病大鼠肾小球与肾小管-间质TGFβ1蛋白表达明显高于对照组，各给药组肾组织TGFβ1蛋白表达明显低于模型组，其中以联合组最明显。结论依那普利与灯盏花素联合给药对糖尿病肾脏保护作用优于任一单给药组，其机制部分与其对肾组织氧化应激增加、PKC激活及TGFβ1表达有协同抑制作用有关。     

依那普利对糖尿病大鼠肾脏保护作用的实验研究

目的 研究依那普利对糖尿病大鼠肾脏的保护作用。方法 应用依那普利对糖尿病大鼠进行了１０周治疗,观察了其对糖尿病大鼠肾脏的保护作用。结果 对照组糖尿病大鼠肾小球滤过度,肾血流量,滤过分数及尿白蛋白均较正常对照组明显升高,肾小球基底膜不规则增厚,突触融合。依那普利治疗后糖尿病大鼠ＧＦＲ,ＲＰＦ,ＦＦ及ＵＡ均较糖尿病对照组明显降低,病理学异常不明显。