吲达帕胺微孔渗透泵片的制备与体外释药机制研究

目的 制备吲达帕胺微孔渗透泵片剂并研究其体外释药机制。方法 通过外观观察,测定不同衣膜、片芯、介质等条件变化时的体外释放度,考察其释药机制。结果 吲达帕胺微孔渗透泵片体外释药行为符合零级释药模型;不同衣膜、片芯和渗透压介质对药物释放有显著影响;释放介质的pH值、溶出方法和转速对药物释放无显著影响。结论 该片剂的释药动力主要为衣膜内外的渗透压差,药物在渗透压驱动下经微孔释药。     

小剂量吲哒帕胺联合左旋氨氯地平对老年单纯收缩期高血压的疗效观察

目的观察左旋氨氯地平联合小剂量吲哒帕胺治疗老年单纯收缩期高血压的临床疗效。方法将40例老年单纯收缩期高血压患者分为A组20例,给予左旋氨氯地平片2.5 mg＋吲哒帕胺片1.25 mg,1次/d。B组20例,给于安慰剂同时辅以运动饮食疗法,两组均治疗8周。分别记录治疗前后偶侧血压及24 h平均血压、心率及生化指标。结果 8周后A组降压效果显著,B组降压效果较差。两组治疗前后心率均无明显变化。结论左旋氨氯地平联合小剂量吲哒帕胺组为降低老年单纯收缩期高血压的合理用药。     

吲达帕胺缓释片致严重肝损害

1例59岁女性患者因高血压、高脂血症、糖尿病,先后口服硝苯地平、缬沙坦、阿卡波糖、氟伐他汀及吲达帕胺.3个月后,患者血生化检查显示:ALT93 IU·L-1,ALP 129 IU·L-1,停用氟伐他汀后未见好转.入院后考虑为药物引起的肝损害,经保肝治疗有所缓解.但数月后血生化检查显示:ALT 509 IU·L-1,AST419IU·L-1,ALP 175 IU·L-1,GGT457IU·L-1.考虑为吲达帕胺引起的肝损害.停用吲达帕胺,井给予还原型谷胱甘肽治疗,随后患者肝功能逐渐好转.出院3个月后复查,肝功能基本正常.     

Antihypertensive efficacy of indapamide SR in hypertensive patients uncontrolled with a background therapy: the NATIVE study*

ABSTRACT

Objectives: Antihypertensive monotherapy rarely achieves blood pressure (BP) control. NATIVE (NATrilix SR use in combInation antihypertensiVe thErapy) evaluated indapamide sustained release (SR) in hypertensive patients receiving background therapy.

Research design and methods: Patients remaining hypertensive (systolic BP [SBP], 145–180?mmHg; diastolic BP [DBP], 95–105?mmHg) while receiving an angiotensin-converting enzyme (ACE) inhibitor (n = 709), β-blocker (n = 629), calcium-channel blocker (CCB; n = 493), angiotensin II type 1 receptor blocker (ARB; n = 75), α-blocker (n = 29) or other therapy (n = 6) were enrolled, recruited by physicians from 228 centres in Pakistan. Indapamide SR 1.5?mg was administered daily for 3 months with background therapy. BP was assessed every 2 weeks, and blood glucose and total cholesterol were evaluated at baseline and study end in a patient subgroup. Adverse events were also recorded.

Main outcome measures and results: Of 2073 enrolled patients (49% males; mean age 51 years), 1941 received indapamide SR and background therapy. SBP and DBP decreased significantly (SBP, 166 ± 16?mmHg at baseline vs. 132 ± 12?mmHg at 3 months; DBP, 102 ± 8?mmHg vs. 83 ± 6?mmHg; both p < 0.0001 vs. baseline). Patients uncontrolled with an ACE inhibitor, β-blocker, CCB or ARB achieved an SBP/DBP decrease of 34 ± 15/19 ± 9, 33 ± 17/19 ± 10, 33 ± 15/18 ± 8 or 35 ± 16/20 ± 12?mmHg, respectively (all p < 0.0001). In all, 84% of patients achieved target SBP (≤?140?mmHg) and 61% achieved BP normalisation (SBP <?140, DBP <?90?mmHg). The absence of placebo control may lead to an overestimation of the extent of the BP reduction achieved. Glucose and cholesterol levels were unaffected by indapamide SR. Four percent of patients experienced side-effects, which were mild-to-moderate in severity.

Conclusions: In patients with hypertension despite antihypertensive therapy, indapamide SR significantly reduced BP with a good acceptability profile. Indapamide SR may represent an effective additional therapy for patients who do not achieve BP goals with other antihypertensive agents.     

Treating hypertension by rational use of diuretics: results of the Russian ARGUS-2 study

ABSTRACT

Objective: Insufficient use of diuretics in combination antihypertensive therapy is a main cause of poor blood pressure (BP) control in Russia. The objective of the ARGUS-2 study was to demonstrate that a rational use of a thiazide-like diuretic, indapamide sustained release (SR), alone or in combination, improves BP control in patients with arterial hypertension difficult to control due to isolated systolic hypertension (ISH), diabetes mellitus (DM), chronic nephropathy, or metabolic syndrome.

Methods: The open-label, non-comparative, 3-month study without preliminary washout included 1438 hypertensive patients (mean age: 57.3?±?10.7 years, mean BP: 158.8?±?14.2/93.4?±?10.0?mmHg), with difficult-to-control arterial hypertension and who had never been treated with diuretics previously. Throughout the study, patients received indapamide SR 1.5?mg OD. BP control was defined as <140/90?mmHg for all patients and <130/80?mmHg for those with diabetes mellitus or chronic nephropathy.

Results: Indapamide SR was given as initiation monotherapy to 13.7% of the patients, as substitutive monotherapy to 6.8% of the patients uncontrolled by a previous monotherapy, as additive therapy to 31.9% of the patients uncontrolled by previous monotherapy, and as additive therapy to 47.6% uncontrolled by previous combination therapy without a diuretic. Among included patients 75.7% received also an ACE inhibitor or an angiotensin II receptors blocker, 43.9% a calcium channel blocker, and 32.8% a beta-blocker. In 3 months after indapamide SR administration, average BP level decreased to 131.8?±?9.7/80.5?±?6.9?mmHg and 84.5% of the study population achieved BP control. BP was controlled in 91.9% of patients with ISH (n?=?477), 74.8% of those with diabetes (n?=?214), 75.6% of those with chronic nephropathy (n?=?82), and 85.1% of patients with metabolic syndrome (n?=?745). No case of hypokalemia was reported.

Conclusion: The study demonstrates the value of including the thiazide-like diuretic indapamide SR in a combined antihypertensive regimen to control BP in hypertensive patients with added cardiovascular risk factors whose hypertension is difficult to treat. Methodological limitations of this study are its open-label design and the possibility of a change in concomitant antihypertensive treatment during the study.     

依那普利联合吲达帕胺治疗糖尿病合并高血压的临床分析

目的 观察依那普利与吲达帕胺联合治疗老年2型糖尿病合并高血压的临床疗效.方法 将99例确诊糖尿病合并高血压的患者随机分为2组;依那普利加吲达帕胺治疗组50例,单用依那普利治疗组49例.治疗12周比较2组治疗前后的降压效果、血浆内皮素-1及血清钾、降糖疗效.结果 依那普利加吲达帕胺组的降压效果和降低血浆内皮素-1方面要优...     

Large volume injection of 1-octanol as sample diluent in reversed phase liquid chromatography: application in bioanalysis for assaying of indapamide in whole blood

Large volume injection of samples in strong diluents immiscible with the mobile phases used in reversed phase liquid chromatography (RPLC) has been recently introduced in practice. In the present work, the potential of the technique has been evaluated for bioanalytical applications. The process consists of the liquid-liquid extraction of indapamide from whole blood into 1-octanol, followed by the direct injection from the organic layer into the LC. Detection was made through negative electrospray ionization (ESI) and tandem mass spectrometry (MS(2)). The method was developed, validated, and successfully applied to a large number of samples in two bioequivalence studies designed for indapamide 1.5mg sustained release and 2.5mg immediate release pharmaceutical formulations. The performance of the analytical method is discussed based on data resulting from the validation procedure and the completion of the bioequivalence studies.     

Long-Term Effectiveness of Indapamide in Hypertension: Neural,Renin and Metabolic Responses

Indapamide conferred effective blood pressure control over the six-month period of study. Blood sugar was elevated slightly in some patients. Hypokalemia occurred commonly within four to six weeks of initiating therapy and was corrected with oral potassium supplementation. There were no changes in cholesterol or triglyceride. There was an increase in plasma renin activity, probably diuretic induced. The antihypertensive efficacy and the low side effect profile may both be related in part to the observed net reduction in neural tone.     

伊贝沙坦联合吲哒帕胺对原发性高血压的疗效及左室肥厚的逆转作用

目的观察伊贝沙坦与吲哒帕胺联用降压疗效及对原发性高血压（EH）左室肥厚（LVH）的逆转作用。方法将82例EH伴LVH患者随即分为A组（单用伊贝沙坦）40例，B组（伊贝沙坦与吲哒帕胺联用）42例。观察两组治疗前后及两组闯血压及LVH指标的变化。结果6个月后两组血压均较治疗前明显下降（P〈0．01），组闻降压幅度差异无显著性意义（P〉0．05），两组左室重量指数均较治疗前明显降低（P〈0．01），B组较A组更明显（P〈0．05）．结论伊贝沙坦联合吲哒帕胺能有效地控制血压且对EH的LVH有逆转作用。