盐酸伊托必利分散片溶出度与稳定性考察

目的比较盐酸伊托必利分散片与普通片的溶出度及稳定性。方法采用桨法测定溶出度,紫外分光光度法在258nm处测定吸光度,计算溶出度,并进行稳定性研究。结果盐酸伊托必利分散片与普通片在5min的累积溶出度分别为81.73%±1.15%和13.86%±0.5%,30min的累积溶出度分别为93.29%±0.12%和74.54%±0.4%。盐酸伊托必利分散片的溶出度和稳定性优于普通片。结论盐酸伊托必利分散片溶出度高、质量稳定。     

反向高效液相色谱法测定盐酸伊托必利颗粒血药浓度及其人体药动学和生物等效性分析

目的:测定人血浆中盐酸伊托必利颗粒的血药浓度并对其在健康人体内的药代动力学及生物等效性进行分析.方法:采用反相高效液相色谱法(RP-HPLC)测定20名男性健康志愿者单剂量口服100mg盐酸伊托必利颗粒剂(受试药)和盐酸伊托必利片(参比药)后,血浆中伊托必利浓度变化情况,用3P97程序进行药代动力学分析.结果:测得受试药和参比药Cmax分别为594.8±152.3和628.6±261.4μg·L-1,Tmax分别为0.766±0.213和0.900±0.392 h,T1/2ke分别为3.21±0.86和3.49±0.77 h,AUC0-15分别为2266.0±1340.9和2339.4 ±1831.7μg·L-1·h-1,AUC0-∞分别为2472.1±1800.3和2496.9±1952.3μg·L-1·h-1.结论:盐酸伊托必利颗粒的相对生物利用度为106.9%±27.3%:选择Cmax、AUC0-15和AUC0-∞进行三因素方差分析与双单侧t检验,结果表明受试药与参比药具有生物等效性.     

卡维地洛胃内漂浮片在Beagle犬内的药动学研究

目的 研究自制卡维地洛胃内漂浮片在Beagle犬体内的药物动力学.方法 6只Beagle犬分别单剂量服用25mg自制卡维地洛胃内漂浮片和市售卡维地洛分散片,1周后2组交叉给药;采用HPLC荧光法测定犬给药后不同时间的血药浓度.结果 卡维地洛胃内漂浮片、分散片的tmax分别为6、2h;Cmax分别为52.67、123.12μg·L-1,胃内漂浮片的相对生物利用度是分散片的94.2％.结论 卡维地洛胃内漂浮片具有明显的缓释特征,有望达到延长疗效、降低不良反应的目的.     

盐酸伊托必利分散片的药代动力学及生物利用度研究

目的 :研究健康志愿者单剂口服试验制剂盐酸伊托必利分散片与参比制剂盐酸伊托必利片的药代动力学和相对生物利用度。 方法 :将 18名健康志愿者随机分为两组 ,分别口服试验制剂和参比制剂 10 0 m g,采集服药后 0 .2 5、0 .5、1.0、1.5、2 .0、3.0、4 .0、6 .0、8.0、10 .0、12 .0、2 4 .0 h的血样本 ,采用高效液相色谱法 (HPL C)测定伊托必利经时血浓度。结果 :两种制剂的药 -时曲线符合口服吸收有滞后时间的一级动力学双室模型。试验制剂和参比制剂主要药代动力学参数如下 :t1 /2 分别为 (15 .0± 3.4 1)、(14 .6± 3.13) h,Tmax分别为 (0 .78± 0 .35 )、(0 .78± 0 .35 ) h,cmax分别为 (6 0 1.78± 15 9.2 9)、(6 11.2 2±16 6 .32 ) ng/ m l,AU C0～ 2 4 分别为 (2 72 1.6± 5 77.92 )、(2 6 32 .3± 6 14 .2 7) ng· h/ m l,AUC0～∞ 分别为 (486 0 .6 0± 80 4 .80 )、(46 75 .90± 6 4 5 .0 0 ) ng· h/ m l。试验制剂相对生物利用度为 (10 3.87± 6 .31) %。用 3P97程序统计分析 ,两种制剂各药代动力学参数均无显著性差异 (P>0 .0 5 )。 结论 :试验制剂盐酸伊托必利分散片和参比制剂盐酸伊托必利片具有生物等效性。     

盐酸伊托必利片在健康受试者中的生物等效性研究

目的 评价盐酸伊托必利片的生物等效性。方法 采用 HPLC-MS/MS 测定血浆中伊托必利的浓度。64 例健康受试者(空腹 32 例,餐后 32 例)随机交叉单剂量口服盐酸伊托必利片受试制剂和参比制剂 50 mg,测定不同时间血药浓度,采用 Phoenix WinNonlin 软件对药动学参数进行计算。结果 空腹试验 C_max、AUC_0-t、AUC_0-∞几何均数比值的 90%置信区间分别为 89.42%～118.95%、93.25%～117.27%、92.78%～117.33%;餐后试验 90%置信区间分别为 90.53%～104.83%、96.72%～99.77%、96.76%～99.88%。结论 盐酸伊托必利片受试制剂和参比制剂具有生物等效性。     

紫外分光光度法测定盐酸伊托必利分散片的含量

目的建立盐酸伊托必利分散片含量的紫外分光光度测定法。方法采用紫外分光光度法,以水为空白对照,258nm为测定波长,测定伊托必利的含量。结果伊托必利浓度在1．64～20．5μg／ml范围内线性关系良好（r=0．9997,n=7）,平均加样回收率99．94％。结论该法操作简便,精密度好,结果可靠,适应盐酸伊托必利分散片含量的快速测定。’     

盐酸伊托必利与多潘立酮片联合治疗功能性消化不良效果观察

目的观察伊托必利与多潘立酮片联合治疗功能性消化不良的效果。方法将116例功能性消化不良患者,随机分成治疗组(盐酸伊托必利+多潘立酮片)62例和对照组(盐酸伊托必利)54例。治疗组每次口服盐酸伊托必利片50mg+多潘立酮片10mg,每日3次,餐前30min服用;对照组口服多潘立酮片10mg,每日3次,两组均连续用药1个月,观察有效率和不良反应发生率。结果治疗1个月后,治疗组的有效率显著高于对照组(P<0.05),而3个月后的复发率显著低于对照组(P<0.05),两组的不良反应发生率和实验室检查无显著性差异。结论盐酸伊托必利与多潘立酮片联合治疗功能性消化不良的效果优于单用多潘立酮片。     

盐酸伊托必利缓释片在犬体内的药动学

目的：对盐酸伊托必利缓释片和分散片在家犬体内进行药动学研究。方法：6只家犬按照单剂量双周期实验设计方案给药，建立一个测定狗血中的伊托必利的高效液相色谱法。结果：2种制剂在体内均符合单隔室一级吸收模型，缓释片和分散片Cmax分别为（548．6&#177;54．2）μg&#183;L^-1和（798．1&#177;42.5）μg&#183;L^-1。tmax分别为（6．7&#177;1．2）h和（1．83&#177;0．25）h，应用3P97药动学程序进行计算，t1/2（Ke）分别为（6．0&#177;0．6）h和（5．72&#177;0．26）h，AUC0→∞分别为（6．6&#177;0．5）mg&#183;L^-1&#183;h和（7．0&#177;0．6）mg&#183;L^-1&#183;h。结论：盐酸伊托必利缓释片具有显著缓释作用。     

胃苏颗粒联合伊托必利对功能性消化不良患者临床研究

目的:探讨胃苏颗粒联合伊托必利对功能性消化不良患者治疗疗效及对胃肠功能和细胞炎性因子影响.方法:选择本院2020年1月—2021年6月收治的功能性消化不良患者120例,按照随机表法分为治疗组与对照组,各60例.对照组患者口服盐酸伊托必利片50 mg/次,3次/d,药物均于餐前30 min服用;治疗组在盐酸伊托必利片基础...     

盐酸伊托必利片的处方筛选及生物等效性研究

目的：筛选确定盐酸伊托必利片的最佳处方,并确定其生物等效性。方法：利用片剂基本性能评价筛选出盐酸伊托必利片合适的处方,再考察体外溶出度,优化出最佳的处方配比。利用其试制药品与参比药品在大鼠体内的药代动力学曲线比较,确定生物等效性。结果：处方确定为盐酸伊托必利50 g,微晶纤维素24 g,乳糖40 g,羧甲淀粉钠7 g,1%羟丙甲纤维素溶液适量,硬脂酸镁0.6 g,制成1000片。试制药与参比药的血药浓度变化趋势基本一致,与参比药品相比具有生物等效性。结论：按照上述处方制成的成品,处方合理,方法简单,便于生产。     

Difference between single and multiple dose pharmacokinetics of orphenadrine hydrochloride in man

Summary Plasma concentrations of orphenadrine were measured by a specific gaschromatographic method in 5 healthy male volunteers after a single oral dose of orphenadrine hydrochloride 100mg. The single dose pharmacokinetic profile of orphenadrine was evaluated from these data. The elimination half-life ranged from 13.2–20.1 h after the commercial tablet formulation. Plasma concentrations, determined in volunteers and patients under different conditions of repeated oral administration of the same formulation of orphenadrine hydrochloride exceeded the theoretical values, predicted from the single dose pharmacokinetics, by a factor 2 to 3. The elimination half-lives after discontinuation of treatment showed a 2 to 3-fold increase over the single dose values. This demonstrates a clear discrepancy between the multiple and single dose pharmacokinetics of orphenadrine. Experiments in dogs suggested competition for biotransformation between orphenadrine and its metabolite N-demethylorphenadrine. Product inhibition of this type could explain the observed discrepancy.     

The physicodynamic properties of mucoadhesive polymeric films developed as female controlled drug delivery system

Phenoporlamine hydrochloride is a novel compound that is used for the treatment of hypertension. The purpose of this study was to develop a sustained release tablet for phenoporlamine hydrochloride because of its short biological half-life. Three floating matrix formulations of phenoporlamine hydrochloride based on gas forming agent were prepared. Hydroxypropyl methylcellulose K4M and Carbopol 971P NF were used in formulating the hydrogel drug delivery system. Incorporation sodium bicarbonate into matrix resulted in the tablet floating over simulated gastric fluid for more than 6 h. The dissolution profiles of all tablets showed non-Fickian diffusion in simulated gastric fluid. Moreover, release of the drug from these tablets was pH-dependent. In vivo evaluations of these formulations of phenoporlamine hydrochloride were conducted in six healthy male human volunteers to compare the sustained release tablets with immediate release tablets. Data obtained in these studies demonstrated that the floating matrix tablet containing more Carbopol was capable of sustained delivery of the drug for longer periods with increased bioavailability and the relative bioavailability of formulation (containing 25% Carbopol 971P NF, 8.3% HPMC K4M) showed the best bioequivalency to the reference tablet (the relative bioavailability was 1.11 ± 0.19).     

盐酸司他斯汀糖浆在健康志愿者体内的生物等效性研究

目的:通过测定健康受试者血清中盐酸司他斯汀浓度,研究不同厂家生产的盐酸司他斯汀制剂的生物等效性。方法:20名健康男性受试者采用体重随机、配对交叉给药方案,分别空腹口服20 mL试验制剂盐酸司他斯汀糖浆和2 mg参比制剂盐酸司他斯汀片,用LC-MS/MS法测定血清中司他斯汀药物浓度,采用DAS 2.1软件计算药动学参数。结果:口服盐酸司他斯汀试验或参比制剂后,盐酸司他斯汀的t1/2分别为(13.09±5.25)和(12.96±4.67)h;tmax分别为(2.9±0.31)和(3.05±0.22)h;Cmax分别为(1 759.6±578.6)和(1 707.1±677.4)pg·mL-1;AUC0~48 h分别为(17 928.6±10 964.4)和(17 388.3±11 154.5)pg.h.mL-1;AUC0~∞分别为(19 940.9±13 237.7)和(19 528.4±14 164.6)pg·h·mL-1。试验制剂的相对生物利用度为(107.0±23.9)%。结论:可以认定试验制剂和参比制剂生物等效。     

Beagle犬灌胃厄多司坦盐酸氨溴索混合物的急性和亚慢性毒性研究

目的 观察Beagle犬给予厄多司坦盐酸氨溴索混合物后出现的急性和亚慢性毒性反应,为临床安全用药剂量的设计和毒副反应监测提供参考.方法 选用Beagle犬进行急性和13周亚慢性毒性试验.急性试验中,设置厄多司坦盐酸氨溴索混合物剂量组(5.04 g/kg)、厄多司坦组(4.80 g/kg)、盐酸氨溴索组(0.24 g/k...     

伊托必利治疗功能性消化不良的临床研究

目的 比较伊托必利与莫沙必利治疗功能性消化不良的疗效和安全性。方法 采用开放随机对照试验、将106例功能性消化不良患者随机分为两组，试验组53例，予伊托必利50mg，饭前服，每天3次；对照组53例，予莫沙必利5mg，饭前服，每天3次，疗程2周。观察症状变化和不良反应，比较治疗前和治疗后上腹各症状积分，进行疗效评估。结果 试验组上腹胀、餐后饱胀、早饱、上腹痛、食欲下降、嗳气和恶心等症状消失或明显政善，积分明显降低（P〈0．01），疗效与莫沙必利相似（P〉0．05）。两组药物不良反应发生率分别为7．5％和9．4％，差异无显著意义（P〉0，05）。结论 伊托必利治疗功能性消化不良近期疗效与莫沙必利相似，安全性好。     

Simultaneous HPTLC Determination of Rabeprazole and Itopride Hydrochloride From Their Combined Dosage Form

A simple, precise, sensitive, rapid and reproducible HPTLC method for the simultaneous estimation of the rabeprazole and itopride hydrochloride in tablets was developed and validated. This method involves separation of the components by TLC on precoated silica gel G60F254 plate with solvent system of n-butanol, toluene and ammonia (8.5:0.5:1 v/v/v) and detection was carried out densitometrically using a UV detector at 288 nm in absorbance mode. This system was found to give compact spots for rabeprazole (Rf value of 0.23 0.02) and for itopride hydrochloride (Rf value of 0.75±0.02). Linearity was found to be in the range of 40-200 ng/spot and 300-1500 ng/spot for rabeprazole and itopride hydrochloride. The limit of detection and limit of quantification for rabeprazole were 10 and 20 ng/spot and for itopride hydrochloride were 50 and 100 ng/spot, respectively. The method was found to be beneficial for the routine analysis of combined dosage form.     

Effects of itopride hydrochloride on plasma gut-regulatory peptide and stress-related hormone levels in healthy human subjects

Itopride hydrochloride (itopride), a gastrokinetic drug, has recently been evaluated for its clinical usefulness in functional dyspepsia. We investigated effects of itopride on human plasma gastrin-, somatostatin-, motilin-, and cholecystokinin (CCK)-like immunoreactive substances (IS); adrenocorticotropic hormone (ACTH)-immunoreactive substances (IS), and cortisol under stress conditions in healthy subjects. A single administration of itopride caused significant increases in plasma somatostatin- and motilin-IS levels compared to placebo. Itopride significantly decreased plasma CCK-IS, and suppressed the ACTH-IS level compared to placebo. We hypothesize that itopride may have an accelerating gastric emptying effect, and a modulatory effect on the hypothalamo-pituitary-adrenal axis and autonomic nervous functions. These effects might be beneficial in stress-related diseases, suggesting that itopride has clinicopharmacological activities.     

盐酸多奈哌齐片人体生物等效性研究

目的进行试验制剂盐酸多奈哌齐片与参比制剂安理申的生物等效性试验,为新药报批及其临床应用提供试验依据.方法用单剂双交叉试验,健康志愿者18名,分别于试验当日晨空腹一次口服试验制剂盐酸多奈哌齐片和参比制剂安理申10mg,采用高效液相色谱法测定盐酸多奈哌齐经时血浓度.结果试验制剂盐酸多奈哌齐片和参比制剂主要药代动力学参数t1/2(β)分别为(54.28±10.14)h和(53.53±9.919)h,Tpeak分别为(3.50±1.15)h和(3.0±1.125)h,Cmax分别为(87±17)ng/mL和(99±23)ng/mL,AUC0～t分别为(2719±1124)ng/mL·h和(3127±1299)ng/mL·h,AUC0～∞分别为(3072±1324)ng/mL·h和(3525±1517)ng/mL·h.试验制剂盐酸多奈哌齐片相对生物利用度为(103.34±14.29)%.结论盐酸多奈哌齐片与参比制剂安理申具有生物等效性,为生物等效制剂.     

盐酸环丙沙星胃漂浮缓释片处方工艺及产业化研究

目的:通过考察各处方工艺影响因素,解决盐酸环丙沙星胃漂浮缓释片产业化问题。方法:以释放性能和漂浮性能为指标,通过考察片剂硬度、颗粒粒度、HPMC用量、HPMC黏度级别、PVP XL用量、NaHCO3用量等,获得成熟的产业化工艺参数。结果:大规模生产所得制剂可在漂浮状态下完全释放药物,释放度试验结果表明产品释放度指标符合标准。结论:盐酸环丙沙星胃漂浮缓释片可使用HPMC,PVP XL,NaHCO3作为骨架材料,并可获得合格工业产品。