马来酸咪达唑仑片在汉族健康人体内的药动学研究

目的:研究马来酸咪达唑仑片在汉族健康人体内的药动学。方法:10名汉族健康受试者口服马来酸咪达唑仑片15mg后,用高效液相色谱法测定咪达唑仑血药浓度,用DAS2.0药动学软件拟合药动学参数。结果:受试者单剂量口服马来酸咪达唑仑片后的主要药动学参数分别为Cma(x103.11±26.37)ng·mL-1、tma(x1.52±0.75)h、t1/(22.96±0.77)h、Vz/F(170.08±50.97)L、CL/F(41.05±12.33)L·h-1、AUC0～1(2368.80±103.37)ng·h·mL-1、AUC0～∞(397.29±124.06)ng·h·mL-1。部分受试者的药-时曲线存在双峰现象。结论:咪达唑仑片的药动学参数个体差异较大,临床应用时应注意个体化给药。     

兰索拉唑肠溶片健康人体药动学研究

目的:研究兰索拉唑肠溶片在人体内的药动学特点。方法:8名健康男性受试者单剂量口服30mg兰索拉唑肠溶片,血样加入内标(奥美拉唑)经预处理后用HPLC-UV法测定。结果:血浆中兰索拉唑浓度在20.00~2 000.00ng.mL-1范围内线性关系良好(r=0.999 9),日内、日间相对标准差均小于10%。主要药动学参数Cm ax为(876.14±278.11)ng.mL-1,tm ax为(3.81±0.70)h,t1/2为(1.68±0.70)h,AUC0~t为(2 925.04±1 110.88)ng.h.mL-1,AUC0~∞为(3 072.88±1 230.40)ng.h.mL-1。结论:本法操作简便,灵敏度高,无杂质峰干扰,测得的药动学参数可为其临床应用提供参考。     

高效毛细管电泳法测定血浆中兰索拉唑对映体浓度

目的建立测定血浆中兰索拉唑对映体浓度的高效毛细管电泳分析方法,并用于兰索拉唑在人体内立体选择性药代动力学研究。方法用乙醚作提取溶剂提取血浆中兰索拉唑。采用高效毛细管电泳法测定6名健康男性受试者经口给予兰索拉唑片后不同时刻血浆中药物对映体浓度,绘制血药浓度-时间曲线,并计算主要药动学参数。结果 S—与R—兰索拉唑对映体的主要药动学参数如下:ρmax分别为(0.538±0.039)mg.L-1和(1.050±0.250)mg.L-1,tmax为(1.8±0.7)h和(1.8±0.7)h,t1/2分别为(1.6±0.7)h和(2.7±1.0)h,用梯形法计算,AUC0-t分别为(1.49±0.36)mg.h.L-1和(4.35±1.52)mg.h.L-1。结论兰索拉唑两对映体在人体内的代谢过程具有立体选择性。     

西嗪伪麻缓释片多次给药后伪麻黄碱的人体药动学研究

目的:研究健康受试者多次口服国产西嗪伪麻缓释片后伪麻黄碱的药动学特点。方法:10名健康受试者(男女各半),每次空腹口服西嗪伪麻缓释片(含伪麻黄碱120mg)1片,bid,连续6d。应用液-质联用(LC-MS)法测定血浆中伪麻黄碱浓度,所测数据用DASver2.0程序处理,然后进行药动学研究。结果:多次口服西嗪伪麻缓释片后伪麻黄碱主要药动学参数为t1/2(6.06±0.67)h,tmax(3.90±0.99)h,Cmax(272.03±52.56)ng·mL-1,CL(58.70±16.80)L·h-1,Vd(255.30±71.20)L,AUC0～36(3419.70±750.80)ng·h·mL-1,AUC0～∞(3422.20±751.00)ng·h·mL-1,MRT0～36(9.45±0.61)h,MRT0～∞(9.47±0.61)h。多次口服受试制剂3d后,伪麻黄碱血药浓度达稳态,其稳态药动学参数为Cssmax(272.03±52.56)ng·mL-1,Cssmin(104.99±37.15)ng·mL-1,Cssav(198.55±38.95)ng·mL-1,DF(0.86±0.20),AUCss(2382.61±467.44)ng·h·mL-1。以上参数男女比较均无显著性别差异,另多次和单次给药所得药动学参数比较均无统计学意义。受试者服药期间未出现明显不良反应。结论:西嗪伪麻缓释片中伪麻黄碱有明显的缓释效果;多次给药后伪麻黄碱的药动学过程无明显改变,在正常人体内无蓄积。     

注射用兰索拉唑在健康人体内单、多剂量的药动学研究

目的研究注射用兰索拉唑在中国健康人体内的单、多剂量药动学。方法24名健康志愿者随机分为3组,每组8人(男女各半),分别恒速静脉注射15、30、60 mg兰索拉唑进行单剂量药动学研究,30 mg剂量组继续给药,qd×7d,进行多剂量药动学研究。按试验方案采血,用高效液相色谱法测定血药浓度,DAS 2.0程序计算药动学参数。结果健康受试者单剂量给药15、30、60 mg兰索拉唑后主要的药动学参数分别为t_(max)(0.669±s 0.014)、(0.667±0.012)、(0.668±0.013)h;c_(max)(1.01±0.05)、(1.69±0.06)、(3.01±0.08)mg·L~(-1);AUC_(0～t)(3.8±0.3)、(6.5±0.3)、(10.26±0.24)mg·h·L~(-1);t_(1/2)(1.8±0.6)、(3.4±0.8)、(2.5±0.5)h。多剂量给药30 mg达稳态时,主要的药动学参数为t_(max)(0.668±0.011)h;c_(max)(1.74±0.05)mg·L~(-1);c_(min)(0.125±0.012)mg·L~(-1);AUC_(?)(6.5±0.3)mg·h·L~(-1);t_(1/2)(3.0±0.9)h;CL (3.8±0.4)L.h~(-1);c_(av)(0.271±0.014)mg·L~(-1);DF(6.0±0.4)%。结论兰索拉唑在连续多次给药后,体内无蓄积现象,血药浓度d4已达稳态。兰索拉唑剂量的增加与C_(max)、AUC_(0～1)和AUC_(0～∞)的增加呈正相关关系;兰索拉唑的体内过程在男女性别间无显著差异。     

2种头孢地尼制剂在健康人体内的生物等效性研究

目的:研究国产头孢地尼分散片和进口头孢地尼胶囊在健康人体内的药动学和生物利用度,评价二者的生物等效性。方法:20名男性健康志愿者随机交叉单剂量口服受试制剂(国产)或参比制剂(进口)200mg后,采用高效液相色谱法测定人血浆中头孢地尼的浓度,以DAS3.0程序计算药物的药动学参数。结果:受试制剂与参比制剂的主要药动学参数分别为:cmax(1.818±0.544)、(1.900±0.560)ng·mL-1,tmax(3.800±0.750)、(3.925±0.766)h,AUC0～12h(9279.7±2650.3)、(9977.9±2949.3)ng·h·mL-1,AUC0～∞(9639.9±2768.0)、(10304.4±3077.4)ng·h·mL-1。受试制剂相对生物利用度为(95.5±24.3)%。结论:受试制剂与参比制剂具有生物等效性。     

2种氯诺昔康制剂的人体药动学及生物等效性研究

目的:研究2种氯诺昔康制剂在人体内的药动学及生物等效性。方法:20名健康男性志愿者随机交叉单剂量口服氯诺昔康颗粒(受试制剂)与氯诺昔康片(参比制剂)8mg后,采用高效液相色谱-电喷雾串联质谱法测定其血药浓度,并用DAS软件计算药动学参数及评价二者生物等效性。结果:受试制剂与参比制剂药动学参数分别为:Cma(x1331±192.1)、(1366±220.5)ng·mL-1,tma(x2.20±0.30)、(2.28±0.60)h,AUC0～2(46264±1581)、(6460±1535)ng·h·mL-1,AUC0～∞分别为(6379±1671)、(6571±1599)ng·h·mL-1,受试制剂相对于参比制剂的生物利用度为(97.5±11.9)%。结论:2种氯诺昔康制剂具有生物等效性。     

复方盐酸曲马多人体药动学研究

目的:研究复方盐酸曲马多的人体药动学。方法:10名健康志愿者口服复方盐酸曲马多1片(每片含盐酸曲马多37.5mg,对乙酰氨基酚325mg),用高效液相色谱-荧光法测定血浆中曲马多的浓度,计算药动学参数。结果:口服复方盐酸曲马多片1片后AUC0~24为(1361.61±441.79)ng·h·mL-1,AUC0~∞为(1555.04±582.51)ng.·h·mL-1,Cmax为(134.81±33.96)ng·mL-1,tmax为(1.9±0.57)h,t1/2为(7.63±2.02)h。结论:本方法可用于复方盐酸曲马多人体药动学研究。     

兰索拉唑钠对映体在犬体内的药动学研究

摘要：目的:研究注射用兰索拉唑钠在犬体内的立体选择性药动学。方法:6只Beagle犬静脉注射兰索拉唑钠,于给药前及给药后5,15,30,45 min及1,1.5,2,2.5,3,4,6 h自犬后肢静脉取血约3 ml制备血浆。采用HPLC法的两种色谱条件对其中的药物含量进行测定。结果:犬静脉注射兰索拉唑钠后,兰索拉唑钠左旋体与右旋体的主要药动学参数为:半衰期(t1/2):（0.434±0.101）,（0.524±0.128） h;清除速率常数（Ke）:（1.695±0.516）,（1.402±0.397） L·h-1;表观分布容积（Vd）:（0.244±0.042）,（0.284±0.048） L·kg-1;清除率（CL）:（0.404±0.093）,（0.390±0.094） L·h-1·kg-1; AUC0～6h:（1.836±0.435）,（1.909±0.440） mg·L-1·h。结论:兰索拉唑钠在Beagle犬体内代谢迅速,兰索拉唑中左旋体及右旋体AUC0～6h的比值是0.96,未发现左旋体与右旋体之间存在明显的相互转化。     

2种硫酸氢氯吡格雷片在健康人体内的药动学及生物等效性研究

目的:研究国产与进口硫酸氢氯吡格雷片在健康人体内的药动学特征及生物等效性。方法:采用标准两周期交叉设计自身对照试验方法,20名健康志愿者单剂量口服硫酸氢氯吡格雷片受试制剂(国产)或参比制剂(进口)75mg后,用液-质联用(LC-MS)法测定人血浆中氯吡格雷的浓度,计算其药动学参数并评价2种制剂的生物等效性。结果:受试制剂与参比制剂的各主要药动学参数分别为:tmax(0.64±0.21)、(0.68±0.27)h,cmax(1.724±1.38)、(1.752±1.856)ng·mL-1,t1/2(6.6±4.9)、(6.3±7.0)h,AUC0～36h(1.996±1.223)、(2.112±1.493)ng·h·mL-1,AUC0～∞(2.114±1.209)、(2.117±1.500)ng·h·mL-1。受试制剂相对于参比制剂的生物利用度为(108.9±52.2)%。结论:2种硫酸氢氯吡格雷片具有生物等效性。     

兰索拉唑肠溶胶囊在健康人体的生物等效性

目的评价2种国产兰索拉唑肠溶胶囊制剂(抗溃疡药)的生物等效性。方法 24例健康成年男性受试者随机分组,按照自身对照的方法单次口服兰索拉唑肠溶胶囊30 mg,用LC-MS/MS测定兰索拉唑和其代谢物5-羟基兰索拉唑、兰索拉唑砜的浓度,用非房室模型方法计算主要药代动力学参数。结果参比制剂和试验制剂的主要药代动力学参数如下。兰索拉唑:t1/2分别为(2.10±1.58),(2.18±1.85)h;tmax分别为(2.20±1.10),(2.00±1.01)h;Cmax分别为(1160.8±550.3),(1232.3±628.1)ng.mL-1;AUC0-t分别为(4963.7±4233.4),(4947.0±4669.3)ng.mL-1.h;AUC0-∞分别为(5027.4±4256.9),(5036.0±4751.2)ng.mL-1.h。5-羟基兰索拉唑:t1/2分别为(1.95±1.20),(1.75±1.00)h,tmax分别为(2.10±1.20),(1.80±1.00)h,Cmax分别为(106.2±61.2),(114.5±61.0)ng.mL-1,AUC0-t分别为(279.1±124.2),(27...     

Effects of lansoprazole plus amoxycillin on the cure of Helicobacter pylori infection in Japanese peptic ulcer patients

Aim : The effect of lansoprazole plus amoxycillin on curing Helicobacter pylori infection and peptic ulcer recurrence was evaluated.
Method : The study group was composed of 68 patients with gastric ulcers and 51 with duodenal ulcers, all were H. pylori -positive. The participants were assigned at random to the lansoprazole alone group (lansoprazole 30 mg o.m. for 6 or 8 weeks) or the lansoprazole plus amoxycillin group (lansoprazole alone regimen plus amoxycillin at 500 mg q.d.s. concomitantly for the first 2 weeks). Healed patients were not given maintenance treatment with acid secretion inhibitors. The cure rate for H. pylori infection and the ulcer recurrence rate after 1 year were investigated.
Result : The cure rate for H. pylori infection was 4.2% in patients receiving lansoprazole alone and 38.5% in patients receiving lansoprazole plus amoxycillin ( P < 0.01) for gastric ulcers, and 0% in patients receiving lansoprazole alone and 61.9% in patients receiving lansoprazole plus amoxycillin ( P <0.001) for duodenal ulcers. The recurrence rate was 42.3% in patients receiving lansoprazole alone and 28.6% in patients receiving lansoprazole plus amoxycillin for gastric ulcers, and 66.7% for patients receiving lansoprazole alone and 11.1% for patients receiving lansoprazole plus amoxycillin ( P <0.001) for duodenal ulcers. None of the patients with gastric or duodenal ulcers cured of H. pylori infection had a recurrence.
Conclusion : Concomitant use of lansoprazole and amoxycillin increased the curative effects on H. pylori infection. However, the cure rates with this regimen remained inadequate.     

Lansoprazole pharmacokinetics differ in patients with oesophagitis compared to healthy volunteers

AIM: To compare the pharmacokinetics of lansoprazole in patients with reflux oesophagitis and in healthy volunteers, after a single dose and at steady-state. PATIENTS AND METHODS: A 30 mg dose of lansoprazole was administered orally daily for 7 days in eight healthy male volunteers aged 21-24 years, and in 16 patients aged 29-65 years with grade 2 or 3 reflux oesophagitis. The pharmacokinetics were assessed over the 24 h dose interval following the first dose and again after the 7th dose. RESULTS: Within both the patient and volunteers groups, there were no significant differences between day 1 and day 7 in any of the pharmacokinetic parameters including maximum concentration (Cmax), area under the concentration-time curve (AUC), and terminal half-life of elimination (t(1/2)). However, on both days 1 and 7, values were significantly higher in the patients than in the healthy volunteers. On day 7, Cmax was 1343 ng/mL in patients compared with 765 ng/mL in healthy volunteers, AUC was 3458 ng.h/mL vs. 1350 ng.h/mL and t(1/2) was 1.62 h vs. 0.90 h. CONCLUSION: The differences in results for the pharmacokinetics reflect reduced lansoprazole clearance in the patient group. Other research has not found a difference in pharmacokinetics when comparing healthy volunteers with patients with acid-related disorders. The difference in lansoprazole clearance in this study may be related to a variety of factors that are different in patients compared with young normal volunteers, such as age, gender, other drugs, and reduced general well-being.     

Pharmacokinetic interaction between proton pump inhibitors and roxithromycin in volunteers

BACKGROUND: Triple therapy including two antibiotics and a proton pump inhibitor is a rational approach to the treatment of Helicobacter pylori induced peptic ulcer disease. The interaction of antimicrobial therapy and acid suppression is not yet well elucidated. AIMS: To investigate the effects of proton pump inhibitors on roxithromycin levels in plasma and gastric tissue under steady-state conditions in volunteers. METHODS: In two crossover studies omeprazole 20 mg b.d., lansoprazole 30 mg b.d., roxithromycin 300 mg b.d., and the combination of roxithromycin with either omeprazole or lansoprazole were administered to 12 healthy volunteers over 6 days. Blood plasma levels of the drugs were measured. In addition, roxithromycin concentrations were also determined in gastric juice and gastric tissue obtained during endoscopy. RESULTS: The proton pump inhibitors and roxithromycin did not alter the blood plasma pharmacokinetics of each other. When compared to roxithromycin administered alone, its combination with a proton pump inhibitor significantly increased the roxithromycin concentrations in gastric juice (3.0-5.0 microg/mL vs. 0.3-0.4 microg/mL) and gastric tissue (antrum: 3.8-4.0 vs. 2.8 microg/g, fundus: 5.9-7.4 vs. 4.2-4.4 microg/g). CONCLUSIONS: Proton pump inhibitors and roxithromycin do not alter the systemic bioavailability of each other. However, proton pump inhibitors increase the local concentration of roxithromycin in the stomach which may contribute to the clinically proven synergic beneficial action in eradication therapy of H. pylori.     

注射用兰索拉唑在健康人体内的药动学研究

目的研究兰索拉唑在健康受试者体内的药动学过程。方法采用三交叉拉丁方设计,12名健康受试者分别静脉滴注兰索拉唑15、30、60 mg(45 min滴完),洗脱期为1周。血浆中兰索拉唑的浓度以HPLC-UV法测定,以DAS Ver 2.1计算药动学参数。结果受试者静脉滴注兰索拉唑后体内过程符合二室模型,单次给药15、30、60 mg后主要药动学参数:t1/2分别为(1.76±1.43)、(1.21±0.4)、(1.86±1.29)h,Cmax分别为(0.92±0.33)、(2.05±0.59)、(4.04±0.55)μg.mL-1,AUC0-10h分别为(3.41±2.14)、(6.25±3.55)、(11.65±5.96)μg.h.mL-1,AUC0-∞分别为(7.67±6.37)、(9.21±7.13)、(14.68±10.01)μg.h.mL-1,V分别为(5.95±5.18)、(6.32±3.74)、(5.26±6.03)L,CL分别为(3.98±4.38)、(4.81±2.18)、(5.43±2.43)L.h-1。结论中国健康受试者单剂量静脉滴注兰索拉唑后,在15~60 mg内的体内过程呈线性药动学特征。兰索拉唑在人体的代谢存在较大的个体差异,变异来源可能与CYP2C19的基因多态性有关,临床宜个体化用药。     

Gastric acidity and acid breakthrough with twice-daily omeprazole or lansoprazole

BACKGROUND: In patients with severe gastro-oesophageal reflux disease (GERD), proton pump inhibitors are being used increasingly in twice-daily regimens to improve control of gastric acidity. Few data exist to compare the ability of the most-often used proton pump inhibitors, omeprazole and lansoprazole, to control gastric acid at twice-daily dosage regimens. Nocturnal acid breakthrough, defined as gastric pH < 4.0 continuously for > 60 min, may compromise treatment goals in patients with GERD. AIM: To compare the effects of omeprazole 20 mg b.d. or lansoprazole 30 mg b.d. on gastric acidity and the relative ability of each dosage regimen to prevent acid breakthrough. METHODS: In a crossover pharmacodynamic study, 20 healthy volunteers (10 male, 10 female, mean age 38 years) were given omeprazole 20 mg b.d. or lansoprazole 30 mg b.d. for 7 days each, in a randomized manner. Each dosage regimen was separated by a minimum 7-day period where no medication was administered. On day 7 of each regimen, 24-h intragastric pH-metry was performed. The percentage of time for which gastric pH was below 4.0 and 3.0, the occurrence of daytime and nocturnal acid breakthrough, and the duration of action of each regimen were compared. Non-parametric statistics for paired data were used. RESULTS: The percentage time for which gastric pH was below 4.0 was significantly lower with omeprazole 20 mg b.d. (median 14.8%) than with lansoprazole 30 mg b. d. (median 24.2; P=0.0372). Fourteen subjects showed more effective acid control when taking omeprazole; these were significantly more often H. pylori-negative patients compared with those for whom acid control was better on lansoprazole (P < 0.001). Nocturnal acid breakthrough occurred in seven patients (35%) on omeprazole and in 10 (50%) on lansoprazole (N.S.). CONCLUSION: In healthy volunteers, twice-daily dosing of omeprazole 20 mg b.d. appears to be significantly more effective than lansoprazole 30 mg b.d. in controlling gastric acidity. The clinical importance of such a difference remains to be defined in GERD patients.     

雷尼替丁、兰索拉唑和氢氧化镁铝抗实验性胃溃疡的比较研究

目的 :比较雷尼替丁、兰索拉唑和氢氧化镁铝抗 3种实验性胃溃疡模型的作用。方法 :采用 3种实验性胃溃疡模型 :小鼠水浸应激性胃溃疡、大鼠幽门结扎型胃溃疡、大鼠乙酸烧灼型胃溃疡 ,以溃疡抑制率来比较三药的治疗效果。结果 :3种模型中兰索拉唑有明显的抑制溃疡形成的作用 (P <0 .0 5 ) ,溃疡指数是最低的 ,溃疡抑制率也均高于其他两药。结论 :兰索拉唑对于实验性胃溃疡的作用优于氢氧化镁铝、雷尼替丁     

Delayed-release lansoprazole plus naproxen

A combination package containing delayed-release capsules of the proton pump inhibitor lansoprazole (15 mg once daily) and tablets of the NSAID naproxen (375 or 500 mg twice daily) has been approved for reducing the risk of NSAID-associated gastric ulcers in NSAID-requiring patients with a documented history of gastric ulcer. In a large, 12-week trial in NSAID (including naproxen)-requiring patients with a documented history of gastric ulcer, significantly more recipients of delayed-release lansoprazole 15 mg once daily than placebo recipients were free from gastric ulcer (p < 0.001). At week 12, the percentages of patients who were free from gastric ulcer were 80% with lansoprazole 15 mg and 51% with placebo. In a subgroup analysis of recipients of naproxen (89% received 750-1000 mg/day), the percentage of patients free from gastric ulcer after 12 weeks of treatment was significantly higher with delayed-release lansoprazole 15 mg than with placebo (89% vs 33%; p < 0.001). In NSAID (including naproxen)-requiring patients with a documented history of gastric ulcer, the incidence of treatment-related adverse events in recipients of delayed-release lansoprazole 15 mg once daily was low (7%), and similar to that in recipients of placebo (10%).     

Rapid healing of gastric ulcers with lansoprazole

Background: Lansoprazole is a new proton pump inhibitor which powerfully decreases acid secretion. Methods: We compared the efficacy and short-term safety of lansoprazole against ranitidine in the healing of gastric ulcer. This was a parallel group, comparative multicentre, prospectively randomized, double-blind study which included 250 patients with gastric ulcer, 219 of whom had follow-up endoscopic data. Results: Both lansoprazole 30 mg and 60 mg daily produced significantly more rapid healing of gastric ulcer than ranitidine 300 mg nightly with healing rates after 4 weeks of 78% (P < 0.05), 84% (P < 0.01) and 61%, respectively. After 8 weeks, the corresponding healing rates were 99%, 97% and 91% (P = 0.08). Symptom relief was similar for all treatment groups, but fewer antacids were used by patients receiving lansoprazole. Sixty-nine patients experienced 91 adverse events; the incidence, pattern and severity was similar across all three treatment groups. Conclusions: Lansoprazole 30 mg and 60 mg once daily had similar efficacy. Both were superior to ranitidine 300 mg nocte in healing gastric ulcer. The short-term safety profile of lansoprazole was similar to ranitidine. These data indicate that lansoprazole should be used at a dose of 30 mg once daily for the treatment of gastric ulcers.     

兰索拉唑联用达喜治疗胃溃疡的临床疗效分析

目的探讨兰索拉唑联用达喜（铝碳酸镁）治疗胃溃疡临床的疗效。方法选自我院门诊198例胃溃疡的患者,分为治疗组105例,对照组93组,两组根除幽门螺杆菌（H．Pylori）三联治疗方法。1周后,治疗组用兰索拉唑和达喜治疗;对照只用兰索拉唑。1疗程为8周。结果治疗组的痊愈率和总有效率分别为61．91％和93．33％;对照组的痊愈率和总有效率分别为40．09％和80．65％,两组的痊愈率和总有效率比较差异有统计学意义俨〈0．05）。药物未见明显不良反应。结论兰索拉唑联用达喜治疗胃溃疡,疗效较单用兰索拉唑显著。