Effect of food on the pharmacokinetics of budesonide controlled ileal release capsules in patients with active Crohn's disease

AIM: To study the influence of food on the systemic availability of budesonide in patients with active Crohn's disease. METHODS: Eight patients with an established diagnosis of Crohn's disease each received 9 mg budesonide controlled ileal release (CIR) capsules (Entocort capsules) orally on two separate occasions: once in a fasting state and once after a heavy breakfast. For reference, deuterium-labelled ((2)H(8)) budesonide, 0.5 mg, was given intravenously. Plasma concentrations of budesonide and (2)H(8)-budesonide were determined for 12 h, and their pharmacokinetic parameters were calculated. RESULTS: Average systemic availability of budesonide during fasting conditions was 10.7%, area under the curve was 27.5 nmol/L x h and peak plasma concentration was 4.1 nmol/L. Corresponding postprandial values were 13.2%, 27.0 nmol/L x h and 3. 8 nmol/L. Food increased the mean absorption time from 4.5 to 6.8 h (P=0.0012). Body clearance of budesonide was about 25% higher after eating (P=0.0015). CONCLUSIONS: Food had little influence on systemic availability and peak plasma concentrations of budesonide administered in CIR capsules. Absorption was retarded postprandially, likely due to delayed gastric emptying. Budesonide in CIR capsules can be administered at the same dose regardless of prandial status in patients with Crohn's disease.     

Pharmacokinetics of budesonide controlled ileal release capsules in children and adults with active Crohn's disease

BACKGROUND: Systemic glucocorticosteroid therapy is effective in Crohn's disease, but is associated with side-effects. Budesonide has high topical anti-inflammatory activity, but considerably lower systemic activity than other oral glucocorticosteroids. AIM: To evaluate the systemic exposure to budesonide (controlled ileal release capsules) in children and adults with active Crohn's disease, and to assess the suppression of plasma cortisol. METHODS: In an open label study, patients (eight children and six adults) with active Crohn's disease received 9 mg budesonide (Entocort capsules) orally once daily for 7 days. Plasma concentrations were determined on the seventh day of administration, and pharmacokinetic parameters were calculated. For reference, 0.5 mg budesonide was given intravenously separately. Plasma cortisol levels were compared with the pre-treatment baseline values. RESULTS: Systemic exposure to budesonide (AUC0-24 h) after 1 week of oral administration was 41 +/- 21 nmol/L x h (mean +/- s.d.) in children and 35 +/- 20 nmol/L x h in adults. The estimated systemic availability in children was 9 +/- 5% and in adults 11 +/- 7%. The mean plasma cortisol (AUC0-24 h) decreased by 64 +/- 18% in children and by 50 +/- 27% in adults. CONCLUSIONS: The systemic exposure, systemic availability and cortisol suppression after oral administration of 9 mg budesonide were similar in children and adults with active Crohn's disease. Budesonide was well tolerated and no clinically important safety-related findings were identified.     

尼群地平控释片的释放度测定

目的：研究了尼群地平控释片剂（Ａ）的处方、制备工艺及释放速率并与国产普通片（Ｂ）比较。方法：含量测定采用紫外分光光度法,检测波长２３８ｎｍ。线性范围０．２０５～２０．０μｇ·ｍｌ－１,ｒ＝０．９９９９。溶出介质：人工胃液∶异丙醇（５∶１）,旋桨法。结果：采用“多级火箭式原理”制备的控释片具有良好地控释作用,其Ｔ５０、Ｔ８０分别比Ｂ大１０倍左右,而形状参数ｍ相差不大。结论：提示药物进入体内后速释部分能迅速溶解吸收并达有效血药浓度,尔后控释部分逐级释放,使药物作用平稳而持久     

A cortisol suppression dose-response comparison of budesonide in controlled ileal release capsules with prednisolone

AIM: To assess the systemic effect of oral budesonide, given as Entocort controlled ileal release capsules, over a dose range of 3-15 mg/day, compared with that of a moderate dose (20 mg/day) of prednisolone. METHODS: Twenty four healthy subjects were given 3, 9 or 15 mg budesonide or 20 mg prednisolone once daily, or 4.5 mg budesonide b.d., or placebo for 5 days in a randomized, double-blind crossover study. The area under the curve (AUC) of plasma cortisol concentration and the amount of cortisol excreted in the urine were monitored. RESULTS: Both plasma and urine cortisol suppression showed a dose-response for the daily doses of budesonide. Prednisolone, 20 mg, suppressed plasma cortisol (AUC) statistically significantly more than 15 mg budesonide (P = 0.014), and 3 mg budesonide statistically significantly more than placebo (P = 0.010). No difference in AUC was detected between 9 mg and 4.5 mg budesonide b.d. Similar results for budesonide vs. placebo were obtained from urine cortisol excretion data. However, prednisolone affected urine cortisol less than it affected plasma cortisol. CONCLUSION: After 5 days of administration, budesonide controlled ileal release capsules, in both clinical (9 mg/day) and high doses (15 mg/day), affected plasma cortisol less than a moderate (20 mg/day) dose of prednisolone.     

盐酸小檗碱结肠控释微丸的制备和体外释放测定

目的制备盐酸小檗碱结肠控释微丸,并初步研究其体外释放行为。方法采用挤出滚圆法制备盐酸小檗碱微丸,旋转包衣锅Eudragit S100包衣,UV法在不同释放条件下测定释放度。结果及结论盐酸小檗碱结肠控释微丸在体外实验中可满足结肠定位释放的要求,使用该方法制备盐酸小檗碱结肠控释微丸有效、可控。     

布地奈德灌肠用温敏性凝胶的体外释放度及局部滞留性评价

目的：考察布地奈德灌肠用温敏性凝胶的体外释放度及体内滞留性。方法：制备布地奈德温敏凝胶灌肠液，采用动态透析法和高效液相色谱法进行体外释放度研究；以新吲哚菁绿IR820为荧光标记物，昆明小鼠为受试动物，应用小动物活体成像系统检测不同时间点温敏凝胶灌肠液在小鼠体内的滞留情况。结果：含有增溶剂的布地奈德温敏凝胶灌肠液在体外能缓慢并完全地释放，体外释药曲线符合Higuchi方程，12 h释放在80%以上，普通灌肠液12 h的累积释药率不到60%；通过对新吲哚菁绿标记物观察，温敏凝胶剂在体内至少可以停留12 h，普通灌肠液体内4 h时几乎不能观察到荧光信号。结论：布地奈德温敏凝胶灌肠液可延长药物在体内的滞留时间，延缓药物释放。     

Maintenance of Crohn's disease over 12 months: fixed versus flexible dosing regimen using budesonide controlled ileal release capsules

BACKGROUND: It may be possible to achieve more effective management of Crohn's Disease by introducing a flexible dosage regimen sensitive to patients' needs. AIM: Comparison of the efficacy and tolerability of a fixed vs. flexible budesonide controlled ileal release treatment regimen for the prevention and management of relapse in Crohn's disease patients. Budesonide controlled ileal release is an oral formulation which delivers drug directly to disease sites in the ileum and ascending colon, by preventing more proximal release and absorption. METHODS: A randomized, double-blind comparison of a fixed dose of budesonide controlled ileal release (6 mg o.m.) and a flexible dose of budesonide controlled ileal release (3, 6 or 9 mg o.m.) for 12 months, in 143 patients in remission from ileal or ileo-caecal Crohn's Disease. RESULTS: Very low rates of clinical relapse in Crohn's disease were achieved with budesonide controlled ileal release 6 mg o.m. There was no significant difference between the treatment groups with respect to the survival estimate of percentage of treatment failures (flexible group 15%, fixed group 19%; P=0.61). The average consumed dose of budesonide was comparable in both groups (5.8 mg flexible, 6.0 mg fixed). Similar proportions of patients reported adverse events (flexible 100%, fixed 97%). There were 33 serious adverse events (flexible 19, fixed 14) and 13 withdrawals due to significant adverse events (flexible 9, fixed 4). CONCLUSION: Maintenance treatment with budesonide controlled ileal release 6 mg o.m. is well-tolerated and is associated with low rates of clinical relapse in stable Crohn's disease over 12 months. Flexible dosing remains an option for individual patients, but this study has shown no advantage over a standard fixed dosing regimen.     

阿西美辛控释胶囊的研制及释放度研究

采用薄膜包衣制成阿西美辛控释微丸，用此微丸制成含阿西美辛３０ｍｇ的胶囊。测定其释药情况表明，该胶囊可达到预期的控释效果。     

卡比多巴-左旋多巴控释片对帕金森患者睡眠障碍的改善作用

目的 探讨卡比多巴-左旋多巴控释片对帕金森病(PD)患者睡眠障碍的改善作用.方法 选取2013年6月至2015年6月本院神经科收治的伴有睡眠障碍的PD患者69例,随机分为观察组39例和对照组30例.观察组卡比多巴-左旋多巴控释片治疗,对照组艾司唑仑治疗.比较两组治疗前后病情Hoehn-Yahr分期评估差异,对两组进行多导睡眠监测,比较两组睡眠情况,并采用睡眠评价量表(ESS)及匹茨堡睡眠质量指数量表(PSQI)评分评估患者睡眠障碍的改善效果.结果 治疗前,观察组、对照组Hoehn-Yahr分期评估、多导睡眠监测睡眠潜伏期、觉醒次数、觉醒时间、ESS、PSQI评分比较,差异均无统计学意义(P＞0.05);治疗后,观察组Hoehn-Yahr分期评估为(1.49±0.72)级,显著低于对照组(P＜0.05),睡眠潜伏期[(25.40±12.12) min]、觉醒次数[(3.21±2.11)次]、觉醒时间[(30.02±10.05)min]均比对照组显著减少(P＜0.05),ESS、PSQI评分均显著低于对照组(P＜0.05);治疗期间,两组均未出现明显的不良反应.结论 与艾司唑仑卡相比,卡比多巴-左旋多巴控释片治疗PD伴睡眠障碍患者效果更显著,可显著改善患者睡眠障碍,进而提高患者生活质量.     

二氢可待因控释片对晚期癌痛病人镇痛效果临床观察

目的;研究二氢可待因控释片对晚期癌痛病人的镇痛作用。方法：47例经病理学确诊的中晚期癌症病人,采用随机临床试验,二氢可待因控释片,每次60－120mg,每12h一次,日剂量＜240mg,连用7d。资料采用t检验或卡方检验作统计处理。结果：二氢可控释片每12h口服一次,可有效地控制晚期癌症慢性中度以上疼痛,临床镇痛总有效率为100％。主要不良反应有头晕、恶心、呕吐、胃部不适,便秘。结论：二氢可待因控释片对晚期癌痛有明显的镇痛作用,药效持续时间长、不良反应小,使用方便。     

己酮可可碱控释片的制备及体外释放度的考察

目的：研究己酮可可碱控释片的处方工艺。方法：对片芯组成进行考察，采用薄膜包衣技术制备己酮可可碱控释片。利用相似因子对优化处方重现性进行评价。结果：致孔剂用量、渗透促进剂种类和崩解剂用量对释药曲线有明显的影响，自制片符合零级释药特征。结论：该控释片处方及制备工艺简单，重现性好，适合工业生产，同时为水溶性大剂量药物制备成控释片提供了一种新的方法。     

盐酸氨溴索渗透泵控释片的体外释放度考察

目的：研究盐酸氨溴索渗透泵控释片的体外释放度。方法：考察渗透泵在不同介质中的释放情况。结果：渗透泵的释药不随释药环境的改变而改变。结论：盐酸氨溴索渗透泵控释片释药稳定，零级释药明显，具备优良控释制剂的特征。     

晚期癌痛患者在社区应用吗啡经皮自控镇痛的探讨

目的探讨晚期癌痛患者在社区应用吗啡经皮自控镇痛的效果。方法选择本社区2010年6月～2011年6月利用吗啡经皮自控镇痛的晚期癌痛患者27例,设为观察组,与同期采用肌注吗啡和地西泮镇痛的26例患者就镇痛效果与患者满意度进行比较。结果观察组在给予镇痛治疗1、3、7、10d后VAS评分明显低于对照组,两组比较差异具有统计学意义,P〈0.05。观察组满意23例,占85.19%;基本满意3例;占11.11%;总体满意率为96.30%;对照组总体满意率为57.69%;两组满意率比较差异具有统计学意义,P〈0.05。结论晚期癌痛患者在社区应用吗啡经皮自控镇痛效果更好,可明显改善患者的生存质量和提高患者的满意度。     

布地奈德雾化吸入对悬雍垂腭咽成形术后咽部水肿及疼痛的作用

目的探讨悬雍垂腭咽成形术后应用布地奈德雾化吸入对咽部粘膜水肿及疼痛的影响。方法对52例阻塞性睡眠呼吸暂停低通气综合征患者行悬雍垂腭咽成形术,随机分为治疗组和对照组,治疗组术后1～6 d应用布地奈德雾化吸入,观察患者咽部水肿及疼痛情况并与对照组进行对比。结果治疗组患者咽部水肿消失在（4.23±0.71）d;对照组患者咽部水肿消失在（5.38±0.70）d;两组差异有显著性。治疗组患者咽部疼痛评分第2天开始较对照组差异有显著性。结论悬雍垂腭咽成形术后患者应用布地奈德雾化吸入可有效减少咽部粘膜水肿及疼痛,值得临床推广。     

Pharmacodynamics of controlled release verapamil in patients with hypertension: an analysis using spline functions

AIMS: To use a nonparametric approach involving longitudinal splines to model the baseline blood pressure profile and investigate the impact of this modelling on the pharmacodynamic analysis for verapamil in patients with angina or hypertension. METHODS: Dose ranging studies were conducted in patients with hypertension and with angina. Subjects received doses of 120, 180, 360 or 540 mg racemic verapamil. Pharmacodynamic data were created by subtracting the (systolic) blood pressure following active drug from the placebo response, either by direct subtraction or after modelling the baseline with a longitudinal spline model fitted to the placebo data by nonlinear mixed effects modelling. An Emax model was then used to describe the relationship between change in blood pressure and (R-)verapamil plasma concentration. RESULTS: The maximum decrease in systolic blood pressure was found to be 57.6 (+/- 26.1) mm and the C50 was 420 (+/- 349) microg/l for the data obtained by direct subtraction of the placebo data. Similar results were obtained when a cubic spline model was used to describe each individual's placebo response. However, the use of a population spline model only allowed a linear pharmacodynamic model to be fitted to the resulting data. Sparse data were created by randomly removing 66% of the data from the placebo and active phases. The population spline model gave very similar parameter estimates for the linear model applied to the sparse data to those obtained from the complete data set. CONCLUSIONS: The use of a longitudinal spline model together with nonlinear mixed effects modelling to account for baseline blood pressure response can be very powerful in a sparse data environment.     

度米芬控释片的研制及其工艺条件的考察

目的:制备度米芬控释片,并对工艺条件进行考察。方法:采用正交设计以体外溶出为指标,对包衣材料种类、包衣剂用量、致孔剂用量进行处方筛选。结果:优化后的结果可以满足中国药典对缓控释制剂体外溶出的要求。结论:该片剂制备工艺简单易行,适合工业化生产。     

布地奈德肠溶缓释微丸的体外释药特性及其在大鼠各肠段的药物残余量

目的制备布地奈德肠溶缓释微丸,并对其体外释药特性和大鼠灌胃后各肠段内容物中药物残余量进行比较研究。方法采用转篮法对制备的布地奈德肠溶缓释微丸进行体外释放度试验,比较微丸在不同释放介质中的释放曲线;测定微丸在大鼠灌胃后各肠段内容物中药物的残余量,并与对照制剂进行比较。结果试验组和对照组微丸在0.1 mol·L~(-1)HCI溶液中2h和PBS 6.8中10 h的释药曲线基本重合,f_2相似因子为90.1;在0.1 mol·L~(-1)HCl溶液12 h的累积释放率均<10%,在PBS 6.0、PBS 6.8和PBS 7.5缓冲液3种介质中12h的释药曲线f_2相似因子分别为54.2、50.3和57.8;两者在大鼠灌胃后2、4、6、8h各肠段残余总量和回结肠残余量的P值均>0.05。结论布地奈德肠溶缓释微丸与对照制剂具有相似的体外释药特性,大鼠灌胃后各肠段药物残余量无显著差异。     

均匀设计法制备苦参碱渗透泵型控释片

目的制备苦参碱渗透泵型控释片,同时建立一种新的设计初级渗透泵处方的方法。方法利用均匀设计法得到释放速率与各处方因素间的定量关系,通过回归方程预测合适的处方。结果回归方程的显著性和精度较好,以其为依据制备了苦参碱控释片。结论对于初级渗透泵的处方设计,均匀设计法是可行的方法。     

临床使用缓、控释制剂过程中存在的问题分析

临床上在使用缓、控释制剂过程中常出现给药次数过多或过少以及掰开或嚼碎后服用等错误情况,致使药物不能很好地发挥治疗效果,同时造成不必要的医疗资源浪费。为保障患者安全、有效和合理地使用缓、控释制剂,本文就缓、控释制剂使用过程中存在的常见问题和药学监护点进行总结和分析,以供广大医务工作者参考。     

雷公藤甲素干预前后类风湿性关节炎患者炎症表达、关节肿胀疼痛度的变化

目的 探讨雷公藤甲素干预对类风湿性关节炎患者炎症表达及关节肿胀疼痛度的影响.方法 选择本院收治的72例类风湿性关节炎患者为研究对象,随机分为对照组36例和观察组36例,对照组患者给予口服甲氨喋呤和美洛昔康治疗,观察组患者在对照组治疗的基础上,给予口服雷公藤甲素.比较两组患者治疗前后血沉速度(ESR)、C反应蛋白(CRP)、类风湿性因子(RF)、血清中炎性细胞因子TNF-α及IL-10水平的变化和关节肿胀疼痛度的差异.结果 观察组患者治疗后ESR、CRP、RF、TNF-α、IL-10分别为(35.44±16.64)mm/h、(14.36±9.84) mg/L、(65.36±41.53) IU/ml、(38.14±6.76)pg/ml、(82.55±70.22) pg/ml,对照组分别为(49.22±22.81) mm/h、(22.59±10.58) mg/L、(136.68±95.76)IU/ml、(42.37±5.46) pg/ml、(71.31±69.89) pg/ml,差异具有统计学意义(t=7.25、10.16、15.22、4.78、6.33,P＜0.05);观察组患者治疗后关节压痛数、关节肿胀数、晨僵时间分别为(9.6±6.8)个、(8.5±5.6)个、(36.6±35.8)min,对照组分别为(11.4±6.6)个、(10.3±8.8)个、(65.3±21.5) min,差异具有统计学意义(t=5.62、6.35、9.58,P＜0.05).结论 雷公藤甲素能够有效降低急性炎症指标,抑制炎性细胞因子的表达,缓解关节肿胀、疼痛等临床症状,值得临床进一步推广.