合用尿囊素铝对司帕沙星片生物利用度的影响

目的：研究合用尿囊素铝片对司帕沙星（SPLX）片生物利用度的影响，寻找合用该二药时最佳给药方案。方法：将志愿者分成A、B、C、D4组，分别以不同给药方案给药。A组作为对照组，口服司帕沙星片400mg；B、C、D组分别给药尿囊素铝片400mg，B组志愿者在服用尿囊素铝片的同时服用司帕沙星片400mg；C组志愿者在服用尿囊素铝片前2h服用司帕沙星片400mg；D组志愿者在服用尿囊素铝片前4h服用司帕沙星片400mg。采用HPLC法测定其司帕沙星血药质量浓度，比较其生物利用度的不同。结果：B、C组的生物利用度明显低于A组（P〈0．01），D组的生物利用度与A组差异无显著性（P〉0．05）。结论：给药时间不同可严重影响司帕沙星片的生物利用度，最佳的服药方法应该是服用司帕沙星片后4h再服用尿囊素铝片。     

乳酸司氟沙星片人体生物等效性研究

目的 :研究乳酸司氟沙星片在健康人体内的药代动力学与相对生物利用度 ,以评价其生物等效性。方法 :采用高效液相色谱法测定10名健康志愿者随机交叉口服单剂量 (400mg)乳酸司氟沙星片与参比制剂 (司帕沙星片 )后血浆中司帕沙星的药 -时数据 ,经3p97药代动力学程序拟合 ,计算其药代动力学参数并评价其生物等效性。结果 :乳酸司氟沙星片与司帕沙星片的主要药代动力学参数分别为 :T1/2β= (22 05±1 70)h、(22 23±1 77)h ;Cmax = (1 80±0 16) μg/ml、(1 74±0 16) μg/ml ;Tmax = (4 11±0 68)h、(3 96±0 80)h ;AUC0～t= (49 12±4 53)h/ (μg·ml)、(45 82±5 32)h/ (μg/ml)。乳酸司氟沙星片的相对生物利用度为(107 57±8 47) %。结论 :乳酸司氟沙星片与参比制剂司帕沙星片为生物等效制剂     

3种治疗慢性细菌性前列腺炎方案的成本-效果分析

目的　对 3种治疗慢性细菌性前列腺炎的药物治疗方案进行药物经济学评价。方法　 A组 :司帕沙星片 /黄酮哌酯 ,B组 :阿奇霉素颗粒 /黄酮哌酯 ,C组 :左氧氟沙星胶囊 /特拉唑嗪片。采用成本 -效果分析法对 3种方案进行回顾性分析。结果　 B组方案成本效果比较低 ,而有效率较高。结论　 B方案为最佳方案     

司帕沙星和氧氟沙星随机对照治疗细菌性感染的成本-效果分析

目的:探讨司帕沙星(Sparfloxacin)与氧氟沙星(Ofloxacin)治疗细菌性感染的经济效果. 方法:根据文献选择212例患者,随机分成两组,其中司帕沙星(A组)106例,氧氟沙星(B组) 106例作为对照组,并运用药物经济学方法进行成本-效果分析.结果:A组和B组治疗方案的总成本分别为:505.0元、360.2元,两组治疗方案的痊愈率分别为:74.5%和69.8%, 有效率分别为:91.5%和88.7%,氧氟沙星组的成本-效果比在四个感染系统中均低于司帕沙星.结论:氧氟沙星治疗细菌性感染优于司帕沙星.     

司帕沙星片在健康人体的药动学和生物等效性研究

目的建立HPLC内标法测定血浆中司帕沙星含量,并研究司帕沙星片的相对生物利用度及生物等效性。方法 20名健康志愿者分2组,随机、交叉口服试验制剂与参比制剂的司帕沙星片0.4 g,测定其血药浓度,计算药物动力学参数及生物等效性评价。结果试验制剂与参比制剂血浆中司帕沙星的tmax为(4.68±0.44)和(4.55±0.51)h;Cmax为(1 560.4±243.9)和(1 584.1±273.9)ng.mL-1;t1/2为(20.92±4.85)和(19.81±3.75)h;用梯形法计算AUC0-t为(43 325±12 174)和(44 139±11 815)ng.h.mL-1;AUC0-∞为(45 452±12 884)和(45 999±12 629)ng.h.mL-1。以AUC0-t计算,试验制剂的平均相对生物利用度为(97.9±5.8)%。结论该法操作简便,快速灵敏,可用于测定血浆中的司帕沙星浓度;司帕沙星的两制剂具有生物等效性。     

解脲支原体感染性非淋菌性尿道(宫颈)炎4种治疗方案的成本-效果分析

目的:比较解脲支原体感染性非淋菌性尿道(宫颈)炎不同药物治疗方案的经济效果.方法:将63例患者随机分成4组,分别给予阿奇霉素(A组)、司帕沙星(B组)、克拉霉素(C组)、米诺环素(D组)治疗,运用药物经济学的成本-效果分析方法对其进行评价.结果:4种方案成本依次为110.60元、201.18元、162.75元、84.00元,有效率分别为62.97%,65%,80%,66.67%.结论:C组治疗方案为最佳方案.     

司帕沙星及洛美沙星对老年慢性阻塞性肺病患者茶碱缓释片药动学的影响

目的　研究司帕沙星及洛美沙星对老年慢性阻塞性肺病(COPD)患者茶碱缓释片药动学的影响。方法　36例老年COPD患者口服茶碱缓释片10 0mg ,q8h×9d ,d 4起Ⅰ组18例合用司帕沙星片2 0 0mg ,qd ;Ⅱ组18例合用洛美沙星胶囊4 0 0mg ,q12h。于d 4、10采集血样,采用荧光偏振免疫法检测茶碱的血药浓度,用PKBP N1程序求得药动学参数。结果　合用司帕沙星后茶碱血药浓度较合用前明显升高(P <0 .0 1) ,AUC及cmax差异有高度统计学意义(P <0 .0 1) ;而合用洛美沙星后其血药浓度较合用前稍有升高(P >0 .0 5 ) ,药动学参数除tmax有统计学意义(P <0 .0 5 )外,其余的变化均无统计学意义。结论　司帕沙星对茶碱的药动学有显著性影响,而洛美沙星对茶碱的药动学情况基本上无明显的影响。     

司帕沙星和氧氟沙星随机对照治疗细菌性感染的成本-效果分析

目的:探讨司帕沙星(Sparfloxacin)与氧氟沙星(Ofloxacin)治疗细菌性感染的经济效果. 方法:根据文献选择212例患者,随机分成两组,其中司帕沙星(A组)106例,氧氟沙星(B组) 106例作为对照组,并运用药物经济学方法进行成本-效果分析.结果:A组和B组治疗方案的总成本分别为:505.0元、360.2元,两组治疗方案的痊愈率分别为:74.5%和69.8%, 有效率分别为:91.5%和88.7%,氧氟沙星组的成本-效果比在四个感染系统中均低于司帕沙星.结论:氧氟沙星治疗细菌性感染优于司帕沙星.     

司帕沙星分散片的人体生物利用度研究

目的研究司帕沙星分散片人体内的相对生物利用度。方法18例健康男性受试者交叉口服单剂量司帕沙星分散片(受试制剂)和司帕沙星普通片(参比制剂)各400 mg，用反相高效液相法测定两种制剂在人血清中的司帕沙星浓度。使用SPSS软件对各药物动力学参数进行统计学分析。结果司帕沙星分散片和司帕沙星普通片的AUC0→∞，Cmax，tmax分别为(48.11±4.04) h·μg·mL^-1，(1.51±0.16) μg·mL^-1，(1.86±0.15)h和(47.12±5.23) h·μg·mL^-1，(1.49±0.21) μg·mL^-1，(4.51±0.21)h。司帕沙星分散片相对普通片生物利用度为(102.10±12.01)%。结论两种司帕沙星制剂的的生物利用度程度差异无显著性，司帕沙星分散片吸收较快。     

米索前列醇片在人工流产术前应用的4种给药途径疗效观察

目的观察米索前列醇片在人工流产术前应用的4种不同给药途径的疗效。方法将要求人工流产的女性200例随机分为4组,每组各50例。每组均于人工流产前0.5-1h给予米索前列醇片400μg,A组：空腹口服给药,B组：舌下含服,C组：阴道给药,D组：直肠给药。4组病例进行宫颈扩张情况、患者疼痛程度、手术时间、出血量、药物副反应及人工流产综合征的对比观察。结果在宫颈松弛度、疼痛效果上,A组差于B组,差异有显著性（P〈0.01）,A组差于C、D组,B组优于C、D组,差异均有显著性（P〈0.05）,D组优于C组,但差异无显著性（P〉0.05）。在手术时间、术中出血量方面,A组长于、多于B、C、D组,差异有显著差异性（P〈0.01）,B组短于、少于C、D组,差异有显著性（P〈0.01）,C组与D组相比,后者优于前者,但差异无显著性（P〉0.05）。在人流综合征发生率的比较中,A组多于B组,差异有显著性（P〈0.01）,C、D组少于A组但多于B组,且C组多于D组,但差异均无显著性（P〉0.05）。药物副反应方面,4组比较差异均无显著性（P〉0.05）。结论米索前列醇片局部给药优于口服给药,尤以舌下含服效果肯定、使用方便简捷,值得临床推广应用。     

The effect of staggered dosing of sucralfate on oral bioavailability of sparfloxacin

Aims

To investigate the effect of sucralfate on sparfloxacin absorption when administered concurrently or at strategically spaced dosing times designed to avoid the potential interaction.

Methods

The study was a four-way crossover design where eight healthy Japanese volunteers were randomized to one of four treatment sequences at entry. A 300 mg dose of sparfloxacin was administered alone for treatment A (control). Treatments B, C and D included sucralfate 1.5 g every 12 h for five doses. For treatment B, the fifth dose of sucralfate was administered concurrently with sparfloxacin 300 mg. For treatment C, 300 mg sparfloxacin was given 2 h prior to the fifth dose of sucralfate. Treatment D consisted of sparfloxacin 300 mg given 4 h prior to the fifth dose of sucralfate. Blood and urine samples were collected at predetermined time intervals for 72 h. Sparfloxacin concentrations in plasma and urine and the concentrations of sparfloxacin metabolite in urine were determined by high performance liquid chromatography assays.

Results

Sucralfate administrated concurrently with sparfloxacin decreased the mean AUC(0,∞) of sparfloxacin 2-fold (P < 0.001) and the mean C_max 2.1-fold (P < 0.001) compared with sparfloxacin alone. When sucralfate was administrated 2 h after sparfloxacin, the mean AUC(0,∞) was decreased 1.5-fold (P < 0.01) and the mean C_max 1.4-fold (P < 0.01). Sucralfate did not alter the extent of absorption of sparfloxacin when it was given 4 h after the administration of sparfloxacin. The relative bioavailabilities for treatments B, C and D were 0.50 (95% CI: 0.35–0.65), 0.64 (95% CI: 0.51–0.77), and 0.92 (95% CI: 0.81–1.03), respectively, relative to sparfloxacin alone. The mean percentage of the sparfloxacin dose recovered in urine was significantly lower after sparfloxacin was administered with sucralfate than after sparfloxacin was administered alone or 2 h before the sucralfate dose (P < 0.001). Treatments B, C and D were demonstrated to be equivalent to treatment A in the rate of absorption. The t_max, CL_r and t_1/2 were not significantly affected by sucralfate. The metabolism of sparfloxacin was not altered in the presence of sucralfate.

Conclusions

Oral administration of sucralfate with sparfloxacin or 2 h after sparfloxacin, decreased the extent of sparfloxacin absorption. When both drugs are to be administered together, sucralfate should be administered 4 h after sparfloxacin, allowing thus sufficient time for sparfloxacin absorption prior to the sucralfate dose and thereby minimizing the chance of a significant interaction.     

4种给药方案治疗慢性前列腺炎/慢性盆腔疼痛综合征的成本-效果分析

目的:研究慢性前列腺炎/慢性盆腔疼痛综合征(CP/CPPS)4种药物治疗方案的成本-效果。方法:140例CP/CPPS患者随机分为4组,分别给予百炎净片+坦索罗辛缓释胶囊(A组)、米诺环素微丸+阿夫唑嗪缓释片(B组)、罗红霉素片+甲磺酸多沙唑嗪控释片(C组)、左氧氟沙星片+特拉唑嗪片(D组),运用药物经济学方法进行成本-效果分析。结果:A、B、C、D组成本分别为268·8元、641·8元、660·8元、666·4元;有效率分别为71·4%、91·4%、88·6%、91·4%;成本-效果比分别为3·76、7·02、7·46、7·29;B、C、D组相对于A组的增量成本-效果比分别为18·65、22·79、19·88。结论:CP/CPPS的治疗成本分为抗生素部分与α1受体阻滞药部分,医师应根据患者的以往用药情况、经济状况、身体健康状况等作出最佳选择。     

消化道肿瘤化疗相关性腹泻的治疗研究

目的:探讨消化道肿瘤患者化疗相关性腹泻的治疗方法。方法:62例化疗相关性腹泻患者随机分成3组,A组口服洛哌丁胺,B组皮下注射奥曲肽,C组皮下注射奥曲肽的同时口服培菲康。观察患者治疗前后的KPS评分和腹泻的治疗效果并进行统计学分析。结果:A组患者治疗前后KPS评分无显著性差异,B组和C组治疗后KPS评分明显高于治疗前。治疗后B组KPS评分高于A组低于C组。B组的腹泻治疗效果与A组和C组都有明显差异。结论:奥曲肽对化疗相关性腹泻有较好治疗效果,奥曲肽和培菲康共同应用的治疗效果更加明显。     

质子泵抑制剂预防危重症患者并发应激性溃疡的循证药物经济学评价

目的:评价多种质子泵抑制剂及不同给药方案在预防危重症患者并发应激性溃疡的成本-效果。方法:检索近10年发表的质子泵抑制剂预防危重症患者并发应激性溃疡的文献,采用循证药物经济学评价方法,比较各质子泵抑制剂及不同给药方案在用药7 d后对危重症患者并发应激性溃疡的预防效果并进行成本-效果分析。结果:共收集使用质子泵抑制剂的危重症患者文献病例1225例,分为A组(注射用奥美拉唑40 mg,bid,静滴)、B组(注射用奥美拉唑40 mg,qd,静滴)、C组(奥美拉唑片20 mg,bid,口服)、D组(注射用泮托拉唑40 mg,bid,静滴)、E组(注射用泮托拉唑40 mg,qd,静滴)、F组(注射用埃索美拉唑40 mg,bid,静滴)、G组(注射用兰索拉唑30 mg,qd,静滴)和H组(兰索拉唑片30 mg,qd,口服),其预防应激性溃疡总有效率分别为86.6%,83.3%,90.7%,94.8%,85.0%,94.4%,89.8%,82.9%(P<0.01),成本-效果比分别为15.2,7.9,1.8,17.1,9.5,19.0,7.5,0.9。结论:H组成本-效果比最低,可做为预防危重症患者并发应激性溃疡的较佳选择方案,对不能口服患者,G组方案为最佳方案。     

沙眼衣原体宫颈炎4种药物治疗方案的成本-效果分析

目的:评价沙眼衣原体宫颈炎4种药物治疗方案的成本-效果。方法:对A(阿奇霉素口服)、B(阿奇霉素静脉注射)、C(美满霉素口服)、D(左氧氟沙星+强力霉素口服)4种沙眼衣原体宫颈炎药物治疗方案进行成本-效果分析。结果:A、B、C、D4种方案的成本分别为(645.20±109.56)、(933.10±249.90)、(413.14±38.04)、(489.00±83.60)元;有效率分别为96.2%、98.6%、93.4%、94.1%;成本-效果比分别为6.71、9.46、4.42、5.19;以C方案为参照,A、B、D方案的增量成本-效果比分别为82.88、99.99、108.37。结论:C方案为较佳方案。     

Effects of enteral feeding on the oral bioavailability of moxifloxacin in healthy volunteers

BACKGROUND AND OBJECTIVE: Moxifloxacin is a new generation fluoroquinolone antimicrobial agent used worldwide. In clinical practice in intensive care units, moxifloxacin may be frequently administered through a nasogastric feeding tube. In the absence of an oral liquid formulation and since the multivalent cations contained in enteral feeds may potentially impair absorption of moxifloxacin administered via this route, we studied the effect of concomitant enteral feeding on the pharmacokinetics and tolerability of moxifloxacin administered as a crushed tablet through the nasogastric tube. PARTICIPANTS AND METHODS: This was a single-centre, open-label, randomised, controlled, nonblinded, three-way crossover study. Twelve young healthy volunteers (nine females and three males) aged 20-42 years were included in the study. Each participant received three separate treatment regimens in a randomised fashion: an intact moxifloxacin 400 mg tablet (regimen A, reference treatment), a crushed moxifloxacin 400 mg tablet as a suspension through a nasogastric tube with water (regimen B) and a crushed moxifloxacin 400 mg tablet as a suspension through a nasogastric tube with enteral feeding (regimen C). A washout period of 1-week followed each treatment. Concentrations of moxifloxacin in serum were measured by a validated high-performance liquid chromatography method. Pharmacokinetic parameters were calculated by noncompartmental methods. Additionally, the primary parameters indicative for changes in absorption (area under the serum concentration-time curve from time zero to infinity [AUC(infinity)] and peak serum concentration [C(max)]), were tested for bioequivalence, assuming log-normally distributed data using ANOVA. RESULTS: All moxifloxacin treatment regimens were well tolerated. The AUC(infinity) was slightly, but not statistically significantly, decreased in treatments with regimens B and C. AUC(infinity) (geometric means 39.6 [regimen A] vs 36.1 [regimen B] vs 36.1 mg.h/L [regimen C] and point estimates 91% for B : A and C : A) indicated bioequivalence of the treatments. Bioequivalence criteria of AUC(infinity) and C(max) were met upon retrospective statistical analysis. Likewise C(max) after moxifloxacin administration through nasogastric tube with water (regimen B) and with tube feed (regimen C) were slightly decreased (geometric means 3.20 [regimen A] vs 3.05 [regimen B] vs 2.83 mg/L [regimen C]; point estimates 88% for B : A, and 95% for C : A). They were within the range seen in other studies conducted with oral administration of the drug. No statistically significant differences were observed in time to reach C(max) (t(max); median 1.75 [regimen A] vs 1.00 [regimen B] vs 1.75 hours [regimen C]). Thus, the rate of absorption of moxifloxacin was not affected by administration through a nasogastric tube. This route of ingestion seems to be associated with a slight loss of bioavailability independent of the carrier medium used (water vs enteral feed); no clinically relevant interaction with the multivalent cations contained in the enteral feed was observed, indicating that moxifloxacin and enteral nutrition can be administered concomitantly. CONCLUSION: There was no clinically relevant effect of enteral feeding on the pharmacokinetics of oral moxifloxacin in healthy volunteers. This result has to be evaluated in patients, particularly those from the intensive care unit, who are characterised by severe infectious and/or concomitant diseases that might influence absorption of moxifloxacin.     

Oral bioavailability of posaconazole in fasted healthy subjects: comparison between three regimens and basis for clinical dosage recommendations

BACKGROUND AND OBJECTIVE: Posaconazole is a potent, extended-spectrum triazole antifungal agent currently in clinical development for the treatment of invasive fungal infections. This study was conducted to compare the bioavailability and resulting serum concentrations of posaconazole 800 mg following administration of three different dose regimens to fasting adults. STUDY DESIGN: This was a randomised, open-label, three-way crossover study. METHODS: Subjects fasted 12 hours before and 48 hours after the administration of posaconazole oral suspension (800 mg) given as a single dose (regimen A), 400 mg every 12 hours (regimen B) or 200 mg every 6 hours (regimen C). Plasma posaconazole concentrations were determined for 48 hours after the initial dose and subjects completed a 1-week washout period between treatment regimens. A one-compartment oral model with first-order rate of absorption and first-order rate of elimination was fitted to the plasma concentration-time data. Differences in exposure were investigated by allowing the bioavailability fraction to vary among regimens. STUDY PARTICIPANTS: A total of 18 healthy men were enrolled in and completed the study. MAIN OUTCOME MEASURES AND RESULTS: Posaconazole relative bioavailability was estimated to be significantly different among regimens (p < 0.0001) and increased with the number of doses, such that regimen B/regimen A = 1.98 +/- 0.35, representing a 98% increase, and regimen C/regimen A = 3.20 +/- 0.69, or a 220% increase. With use of the one-compartment model, the population steady-state values for area under the concentration-time curve over 24 hours were predicted to be 3900, 7700 and 12 400 microg.h/L, with average plasma concentrations of 162, 320 and 517 microg/L for regimens A, B and C, respectively. CONCLUSION: These data suggest that divided daily dose administration (every 12 or 6 hours) significantly increases posaconazole exposure under fasted conditions.     

甲泼尼龙在脊柱围手术期中的预防性应用

目的探讨甲泼尼龙（MP）在脊髓减压手术围手术期的预防性应用价值及其与术后神经功能恢复之间的相关性。方法96例患者，包括脊髓型颈椎病40例，脊柱椎管内肿瘤27例，颈胸椎的韧带骨化29例。患者根据不同剂量和用法分为4组，A组：术前0．5h应用MP；B组：术中减压开始后应用MP；C组：患者回病房后开始应用MP；D组：术中、术后均未应用MP，使用常规甘露醇脱水。结果A、B组与D组相比，神经功能恢复有显著性差异；C组与D组比较无显著性差异。所有患者均未发生创口感染、肺部感染和应激性溃疡等并发症。结论术前和术中应用MP能明显提高脊髓型颈椎病、脊柱椎管内肿瘤和韧带骨化性疾病等脊髓减压手术患者术后神经功能的恢复率和手术的安全性。     

海洛因依赖躯体脱毒治疗方案的比较

目的··:寻找一种相对较佳的躯体脱毒治疗方案。方法·· :对符合DSM -Ⅲ -R药物依赖及阿片类戒断反应诊断标准的90例海洛因依赖者随机分成3组 ,即美沙酮替代递减法 (A组 )、阶梯治疗法 (美沙酮口服液 ,盐酸丁丙诺啡注射液和盐酸洛非西定片 ,B组 )、盐酸洛非西定递减治疗 (C组 )3组。采用双盲双模拟的给药方法 ,进行为期15d的治疗比较。戒断症状采用《戒断症状评定量表》、《汉密顿焦虑量表》和《不良反应观察量表》进行评定。结果··:A、B两组d2 -8戒断症状分值无显著性差异(P>0.05) ,C组与A、B两组d2 -8戒断症状分值有显著性差异(P<0.05)。A组后期戒断症状减分缓慢 ;C组头晕、恶心等不良反应出现较多。结论·· :阶梯治疗法 (B组 )相对较好