润燥止痒胶囊联合咪唑斯汀治疗老年瘙痒症疗效观察

目的:研究润燥止痒胶囊联合咪唑斯汀治疗老年皮肤瘙痒症的疗效。方法:将110例患者随机分为两组,,均患者均服用咪唑斯汀10mg,qd;治疗组加用润燥止痒胶囊4粒/次tid,疗程为4周。结果:治疗2周时治疗组和对照组患者有效率分别为65.51%和28.85%,两组有效率比较差异有统计学意义(P<0.05)。4周时治疗组有效率为91.38%;对照组有效率73.08%,两组比较差异有显著性(P<0.05)。结论:润燥止痒胶囊联合咪唑斯汀治疗老年皮肤瘙痒症疗效明显。     

咪唑斯汀联合肤痒颗粒治疗慢性特发性荨麻疹临床疗效观察

目的评价咪唑斯汀(mizoladtine)联合肤痒颗粒治疗慢性特发性荨麻疹的疗效。方法对慢性特发性荨麻疹患者126例,分为3组,治疗组患者给予咪唑斯汀10mg,1次/d,肤痒颗粒9g,3次/d;对照1组患者给予咪唑斯汀10mg,1次/d;对照2组患者给予肤痒颗粒9g,3次/d;3组患者均以2w为1个疗程,共观察2个疗程。结果108例患者完成实验,第1疗程结束后,治疗组与对照1组和对照2组的治愈率分别为83·8%、73·5%和64·9%。第2疗程结束后,治疗组与对照1组和对照2组的治愈率分别为89·2%、82·4%和64·9%。结论咪唑斯汀联合肤痒颗粒治疗慢性特发性荨麻疹起效迅速,复发率低。     

咪唑斯汀治疗荨麻疹48例疗效观察

以咪唑斯汀治疗荨麻疹,口服1次10mg,14天后其治愈率为81.25%,无明显副反应。     

Can an antihistamine delay appearance of hay fever symptoms when given prior to pollen season?

Mizolastine is a new, nonsedating antihistamine providing satisfactory symptom relief in allergic conditions. The purpose of this study was to determine whether the onset of hay fever symptoms could be delayed in patients known to suffer seasonal allergic rhinoconjunctivitis symptoms if mizolastine was given before the pollen season. This double-blind study involved 342 patients, randomly allocated to once-daily 10 mg mizolastine ( n = 115), once-daily 120 mg terfenadine ( n = 116), or placebo ( n = 111) groups. All patients started treatment on 1 May, before the onset of the grass pollen season. The prophylactic effect of test drugs was assessed on their ability to delay the time to the first hay fever crisis of the season, which was defined by the occurrence of one of the following events: use of rescue medication, study withdrawal because of treatment failure, or total diary symptom score over 18. Active treatments prolonged the time to the first crisis by approximately 1 week (mizolastine 55 days, terfenadine 57 days) in comparison with placebo (50 days) (survival curve analysis: Logrank test, P = 0.01; Wilcoxon test, P = 0.03). Tolerability was satisfactory and comparable between groups. Thus, mizolastine can be safely used to delay and to treat symptoms of seasonal allergic rhinitis.     

复方甘草酸苷联合咪唑斯汀治疗过敏性鼻炎的疗效观察

目的：观察复方甘草酸苷联合咪唑斯汀治疗过敏性鼻炎的疗效。方法：随机将98例过敏性鼻炎患者分为两组,治疗组：复方甘草酸苷20mg,3次/d,口服,咪唑斯汀10mg,1次/d,口服,共治疗15天;对照组：咪唑斯汀10mg,1次/d,口服,共15天;分别在停药时及停药15天后观察疗效。结果：治疗15天停药时治疗组有效率为78.8%,对照组有效率为65.6%;停药15天后治疗组有效率为89.4%,对照组有效率为71.9%。结论：复方甘草酸苷联合咪唑斯汀治疗过敏性鼻炎副作用小,远期疗效好。     

Mizolastine: antihistaminic activity from preclinical data to clinical evaluation

Mizolastine, a new H₁-receptor antagonist, is highly selective for histamine H₁ receptors and has no anticholinergic, antiadrenergic, or antiserotonin activity. It is rapidly absorbed after oral ingestion, with peak plasma concentrations occurring at 1.5 h. The distribution and terminal elimination half-life values are 2 and 13 h, respectively, in healthy young adult volunteers. Half-life values are longer in the elderly and in subjects with chronic renal insufficiency; however, the differences are not large enough to be clinically relevant or to necessitate a dose adjustment in these populations.
  Mizolastine produces prompt, sustained, peripheral blockade of histamine H₁ receptors in the skin. Suppression of the histamine-induced wheal and flare begins 40–60 min after ingestion of a 10-mg dose, peaks at 3–4 h, lasts for at least 24 h, and does not decrease during regular once-daily dosing. The amount of wheal suppression is comparable to that produced by other leading new H₁-receptor antagonists.
  These pharmacokinetic and pharmacodynamic studies of mizolastine provide its clinical pharmacology 'signature'. They also provide the scientific rationale for recommending a once-daily 10-mg dose and suggest that the efficacy and effectiveness of mizolastine will be widely confirmed in allergic disorders, especially rhinitis and urticaria.     

Population pharmacokinetic analysis and optimization of the experimental design for mizolastine solution in children

Mizolastine is a second generation antihistamine agent approved in Europe for the treatment of allergic rhinitis and skin conditions for which SanofiSynthélabo is developing a pediatric solution. Our objective was to design the population pharmacokinetic (PK) study of mizolastine pediatric solution in children. A bioavailability study of this solution compared to the marketed tablet was performed in 18 young volunteers. These PK data were analyzed by nonlinear regression using a two-compartment open model with zero-order absorption. From the estimated parameters, we designed population PK studies in two groups of children: 6 to 12 years and 2 to 6 years, respectively. To compare several population designs and to derive the optimal ones, we used the determinant of the Fisher information matrix of the population characteristics using a first-order expansion of the model. We have evaluated a reference population design with 10 samples (from 0.25 to 36 hr after drug intake) per child in 6 children, which could not be implemented in practice for ethical reasons. We then derived optimal population designs with 1, 2, 3, 4, or 5 samples per child and a total of 60 samples. Finally, the designs that were implemented in the population PK study were compromise population designs with 60 samples; one defined for 20 children 6 to 12 years old , and one with 24 children 2 to 6 years. In the older group, the population design involved 8 children with a catheter from which 6 samples at time 0.25, 0.5, 0.75, 2, 3, and 6 hr after drug intake are collected, and 12 children with only one sample at time 8, 12, 24, or 36 hr. In the younger group, the population design involved 15 children with a catheter who are divided in three groups with four samples at different times from 0.25 to 6 hr after drug intake, and 12 children with only one sample at time 8, 12, 18, or 24 hr. The expected average increase of variances of these designs compared to the reference design were 1.6 and 1.8 for the older and younger group, respectively, which was decided to be acceptable. Better population designs would have involved three groups of children with five samples per child but could not be implemented in practice. The data of the PK study in children 6 to 12 years were available and were analyzed using NONMEM. A total of 53 concentrations were obtained in 18 children. The same two-compartment model with zero-order absorption was used. The interindividual variability in children was small. The estimated population parameters in children 6 to 12 years, were 0.28 L/kg for V_c/F, 0.10 L/hr per kg for CL/F, 0.53 hr^–1 for ₁, 0.076 hr^–1 for ₂ , and 0.49 hr for T _abs . These values were close to the median values observed in young volunteers when standardized to 70 kg; notably, CL/F in L/hr per kg was similar, so that a dose of 0.15 mg/kg o.d. for mizolastine pediatric solution should give an equivalent area under the curve to a 10 mg o.d. tablet in adults.     

咪唑斯汀的合成工艺改进

由4-甲胺基-1-哌啶羧酸乙酯和甲硫尿嘧啶反应后水解脱羧得到的2-[(4-哌啶基)甲胺基]-4(1H-嘧啶酮，与2-氯-1-(4-氟苄基)-1H-苯并咪唑缩合制得咪唑斯汀，总收率49.5％。     

咪唑斯汀缓释片的处方工艺筛选

目的：制备一种能在5h内完全释放的咪唑斯汀缓释片。方法：以体外释放度的测定为主要考察指标，采用单因素筛选法，初步确定缓释片的处方，再对处方进一步的优化调整，确定处方中各辅料的用料量，并对缓释片的工艺在常规方法的基础上进行各项参数的优选，最后将自制缓释片与国外上市产品进行各项体外指标的对比试验。结果：其1000片配方为咪唑斯汀10mg、羟丙甲纤维素（HPMC）11．5mg、酒石酸氢钾40mg、乳糖110mg、微晶纤维素40mg、10％的乙基纤维素（EC）乙醇溶液0．068mL。结论：该处方工艺制备的咪唑斯汀缓释片能达到5h缓释的预期要求，达到了国外该制剂的同等水平，经验证适合扩大生产。