安非他酮缓释片多剂量给药生物等效性研究

目的:研究两种盐酸安非他酮片多剂量给药在健康人体的相对生物利用度,评价安非他酮缓释片剂的生物等效性.方法:采用双周期自身交叉设计,20例健康志愿者多剂量口服受试制剂(安非他酮缓释片剂,每天早晚各150 mg)或参比制剂(安非他酮普通片剂,早晨150 mg,中午和晚上各75 mg),连续给药7 d.用HPLC-MS测定血浆中安非他酮的浓度,并采用BECS程序计算有关药动学参数.结果:受试制剂和参比制剂药动学参数Cmax分别为(123.88±20.80)和(179.40±42.22) μg·L-1;Tmax分别为(2.56±0.89)和(1.19±0.42)h;t1/2分别为(10.61±4.93)和(10.54±6.46)h,AUC0～24 h(ss)分别为(1 076.4±274.2)和(1 041.0±310.6) μg·L-1·h;AUC0～∞(ss)分别为(1 421.1±386.1)和(1 361.8±391.7) μg·L-1·h.以AUC0～24h(ss)计,相对生物利用度为(105.56±14.95)%.两制剂的Tmax有显著性差异.AUC0～24(ss)和AUC0～∞(ss)的90%置信区间在等效范围内.结论:两制剂生物等效.     

盐酸吗啡缓释片与硫酸吗啡缓释片对控制癌性疼痛的临床对比研究

目的：探讨盐酸吗啡缓释片与硫酸吗啡缓释片控制癌性疼痛效果。方法癌症患者146例随机分为两组,口服硫酸吗啡缓释片患者73例为对照组,口服盐酸吗啡缓释片患者73例为观察组,比较癌性疼痛缓解情况及不良反应情况。结果观察组治疗后癌性疼痛状况明显好于对照组（P ＜0.05）。观察组癌性疼痛缓解率高于对照组,观察组恶心呕吐、头痛头晕、嗜睡、便秘、排尿困难的发生率均低于对照组（P＞0.05）。结论盐酸吗啡缓释片控制癌性疼痛的效果更好,并发症少且安全性高。     

硫酸吗啡缓释片辅助治疗癌性疼痛的疗效观察

目的观察硫酸吗啡缓释片辅助治疗癌性疼痛的临床疗效。方法将69例晚期癌症患者随机分为2组,观察组39例,应用硫酸吗啡缓释片;对照组30例,应用盐酸吗啡控释片,30 mg/12 h,2次/d。对比两组的临床疗效。结果观察组疼痛缓解率为92.3%（36/39）,与对照组（70.0%,21/30）比较,差异有统计学意义（P〈0.01）。结论硫酸吗啡缓释片镇痛效果确切,是辅助治疗癌性疼痛的理想药物。     

草酸依地普仑片多次给药药动学研究

目的:探讨健康国人多次口服草酸依地普仑片体内药动学特点。方法:9名健康受试者,每日空腹口服草酸依地普仑片10mg,连续8d,采用高效液相色谱荧光检测法测定血浆中依地普仑浓度,并计算药动学参数。结果:多次口服10mg依地普仑片后药-时曲线符合二室模型,其Cmax,tmax,t1/2,AUC0-132,AUC0-∞,AUCSS,波动度DF,累积系数R分别为(38.0±6.4)μg·L-1,(3.1±1.2)h,(36.8±6.4)h,(1580.0±778.8)μg·h·L-1,(1772.0±804.0)μg·h·L-1,(598.5±124.4)μg·h·L-1,(79.2±27.5)%,(1.51±0.07)。结论:草酸依地普仑多次给药后在健康中国人体内耐受良好,人体内的药动学行为与国外文献报道基本一致。     

Linezolid absolute bioavailability and the effect of food on oral bioavailability.

Linezolid is a novel oxazolidinone antibiotic that has a spectrum of activity encompassing a variety of Gram-positive bacteria. The objectives of this study were twofold: (1) to compare the absorption of linezolid tablets given immediately following a high-fat meal with the absorption of tablets administered while fasting, and (2) to assess the bioavailability of a 375-mg oral dose given while fasting relative to a 375-mg dose of linezolid sterile solution given intravenously. Venous blood samples were taken over the 48 h following the single dose administration of both the oral and intravenous (IV) treatment. Samples were subsequently frozen for the determination of linezolid concentrations by HPLC. The only statistically significant difference between the fasted and the fed treatment was in peak plasma concentration, with the mean C(max) for fasted subjects being 23% greater than that for subjects after consumption of a high-fat meal. Comparable AUC(0-infinity) values were measured under both conditions, indicating that the overall extent of absorption is the same. Therefore, the difference in C(max), while statistically significant, should not affect the therapeutic efficacy of linezolid when it is administered with food. There were no statistically significant differences in AUC(0-infinity), CL or half-life between the fasted oral treatment and the intravenous treatment. As expected, C(max) was statistically different between the two treatments. However, the mean absolute bioavailability (F) of the tablet, using the IV sterile solution as the reference treatment, was 103% (+/-20%).     

多剂量口服硝苯地平缓释片的药动学及生物等效性研究

目的研究多剂量口服硝苯地平缓释片在人体内的药动学特点和两种硝苯地平缓释片的生物等效性.方法22名健康男性志愿者采用双周期交叉、自身对照试验设计.以尼群地平为内标,采用高效液相色谱-大气压化学源-质谱联用(HPLC-MS)的方法,测定人血浆中硝苯地平的浓度.将22名受试者的经时血药浓度录入DAS(ver 1.0)程序,得到药代动力学参数,并进行统计分析和生物等效性评价.结果多剂量口服 20 mg×7 d 受试和参比制剂后血浆中硝苯地平的Cmax分别为 52.5±27.4、54.0±31.2 ng·ml-1,Cmin分别为 5.4±4.1、6.2±5.9 ng·ml-1,Cav分别为 16.8±9.2、19.3±12.4 ng·ml-1,Tmax分别为 3.7±0.9、4.1±1.1 h,t1/2分别为 8.9±4.9、8.5±3.1 h,AUC0-τ分别为 403.4±221.0、461.9±296.6 ng·h·ml-1,AUC0-36h分别为 444.4±256.1、503.1±330.9 ng·h·ml-1,AUC0-∞分别为 482.1±268.9、542.3±348.4 ng·h·ml-1 ,DF分别为(299.8±117.7)%、(279.2±97.5)%.Tmax进行非参数秩和检验,Cmax、Cmin、Cav、DF、AUC0-τ、AUC0-36h、AUC0-∞经对数转换后做方差分析,并经双向单侧t检验,两制剂的Tmax、Cmax、Cmin、Cav、DF、AUC0-τ、AUC0-36h、AUC0-∞均无显著性差异(P＞0.05),受试制剂的Cav、DF、AUC0-36h、AUC0-τ、AUC0-∞的90%可信限落在参比制剂的80%～125%范围内;Cmax、Cmin的90%可信限落在参比制剂的70%～143%范围内.两种制剂的相对生物利用度为(100.6±38.6)%(AUC0-36h,T/AUC0-36h,R×100%).结论两种制剂具有生物等效性.     

The effect of food on the bioavailability of dolasetron mesylate tablets

Anzemet® (dolasetron mesylate) is being developed for the prevention of chemotherapy-induced emesis and postoperative nausea and vomiting. Twenty-four healthy male subjects were orally dosed with dolasetron mesylate, 200 mg, after either an overnight fast or a high-fat breakfast. The ratio of the mean area under the plasma concentration–time curve of the reduced active metabolite (MDL 74 156) to infinity (AUC(0–∞)) values in fed compared to fasting subjects was 86.3% with a 90% confidence interval for the ratio within (80, 125)%, indicating bioequivalence. The ratio of the mean MDL 74 156 maximum plasma concentration (C_max) values was 70.6% in fed versus fasted subjects. The time to C_max was statistically significantly longer after the high-fat breakfast (mean values, 1.11 h fasting and 1.80 h fed), probably due to delayed gastric emptying. It may be concluded that, although the rate of absorption was somewhat delayed, the extent of absorption did not change significantly when dolasetron mesylate was given with food. © 1998 John Wiley & Sons, Ltd.     

盐酸二甲双胍缓释片人体相对生物利用度研究

目的:评价盐酸二甲双胍缓释片与普通片的人体相对生物利用度。方法:采用自身交叉试验设计,18名健康男性志愿者单剂量及多剂量口服盐酸二甲双胍普通片或缓释片,血药浓度采用HPLC-UV法测定。研究盐酸二甲双胍缓释片的相对生物利用度,并对缓释制剂的缓释情况进行评价。结果:盐酸二甲双胍缓释片和普通片单剂量给药后的Cmax分别为(0.779±0.368)和(1.189±0.528)μg/mL;Tmax分别为(2.67±1.26)和(1.56±0.56)h;AUC0→t分别为(7.176±3.134)和(7.006±3.016)μg.h.mL-1。盐酸二甲双胍缓释片的相对生物利用度为(103.38±14.68)%。盐酸二甲双胍缓释片和普通片多次给药后的Cmax分别为(0.783±0.192)和(1.037±0.281)μg/mL;Tmax分别为(3.12±0.58)和(1.56±0.29)h;AUC0→t分别为(6.585±1.647)和(4.158±1.033)μg.h.mL-1;波动度DF分别为(2.71±0.68)%和(2.79±0.56)%。结论:盐酸二甲双胍缓释片(每片含盐酸二甲双胍500 mg)每天1次口服与等剂量市售盐酸二甲双胍普通片每天2次口服具有生物等效性。     

硫酸吗啡缓释片治疗中重度癌性疼痛的临床研究

目的研究用硫酸吗啡缓释片控制中重度癌性疼痛的临床疗效。方法对240例中重度癌性疼痛患者使用硫酸吗啡缓释片进行止痛治疗,初始剂量10～30 mg/次,每12小时用药1次,个体化用药,同时给予辅助药物增强止痛效果,减轻或避免不良反应。结果疼痛缓解率95.8%,平均维持剂量为80 mg/d,最大剂量为360 mg/d,其中47.5%患者不需要增加初始剂量,52.5%增加范围在50%～300%,不良反应均能耐受,无一例出现精神依赖性。结论硫酸吗啡缓释片可以作为中重度癌性疼痛的首选用药。     

Absolute bioavailability and dose proportionality of oral ganciclovir after ascending multiple doses in human immunodeficiency virus (HIV)-positive patients

This study was designed to determine the bioavailability and dose linearity and proportionality of ganciclovir after multiple oral administrations of 3,000 mg to 6,000 mg per day. In an open-label, randomized, four-treatment crossover design, 24 patients seropositive for human immunodeficiency virus (HIV) and cytomegalovirus (CMV) received in random order multiple oral doses of ganciclovir 1,000 mg every 3 hours (six times a day), 1,000 mg four times a day, and 1,000 mg three times a day and a single 5-mg/kg intravenous infusion (over 1 hour) of ganciclovir. Blood samples for pharmacokinetic determinations were obtained on day 3 of each oral regimen and on the day of the intravenous infusion over a 24-hour time interval. Mean steady-state average serum concentrations of ganciclovir were 0.54, 0.79, and 0.99 microgram/mL, respectively, with the 3, 4, and 6 g/day oral regimens. The steady-state area under the concentration-time curve (AUC0-24) for the 6,000 mg/day oral regimen approached that of the single-dose intravenous regimen. There was a proportional increase in AUC0-24 between the 3 and 4 g/day dosage regimens, but not between the 4 and 6 g/day regimens. This suggests nonlinear absorption of ganciclovir at higher dosages, although the departure from proportionality was less than 11%.     

Important effect of food on the bioavailability of oral testosterone undecanoate

STUDY OBJECTIVE: To assess the effects of food on the bioavailability of testosterone undecanoate, testosterone, and 5alpha-dihydrotestosterone (DHT) after administration of a new oral testosterone undecanoate formulation, Andriol Testocaps. DESIGN: Randomized, open-label, crossover study with a 1-week washout period. SETTING: Clinical pharmacology unit. SUBJECTS: Sixteen healthy postmenopausal women. INTERVENTION: Single oral doses of testosterone undecanoate 80 mg were administered either during a fasting period or after consumption of a standardized continental breakfast. MEASUREMENTS AND MAIN RESULTS: Serum concentrations of testosterone undecanoate were assayed by liquid chromatography with mass spectrometry detection; testosterone and DHT were assayed by gas chromatography with mass spectrometry detection. Serum concentrations of testosterone, testosterone undecanoate, and DHT were low to negligible when testosterone undecanoate was administered to subjects in a fasting state; these values were significantly higher when the test drug was coadministered with food. For testosterone, the maximum serum concentration and area under the plasma concentration-time curve were 0.67 ng/ml and 5.37 ng x hr/ml, respectively, in the fasting state, versus 10.7 ng/ml and 56.4 ng x hr/ml, respectively, in the fed state. The same parameters were also significantly higher for testosterone undecanoate and DHT in the fed versus fasting subjects. CONCLUSION: Food increases the bioavailability of testosterone undecanoate, testosterone, and DHT. For proper absorption, Andriol Testocaps must be taken with meals.     

Characterization and evaluation of self-nanoemulsifying sustained-release pellet formulation of ziprasidone with enhanced bioavailability and no food effect

The purpose of this work was to develop self-nanomulsifying drug delivery systems (SNEDDS) in sustained-release pellets of ziprasidone to enhance the oral bioavailability and overcome the food effect of ziprasidone. Preformulation studies including screening of excipients for solubility and pseudo-ternary phase diagrams suggested the suitability of Capmul MCM as oil phase, Labrasol as surfactant, and PEG 400 as co-surfactant for preparation of self-nanoemulsifying formulations. Preliminary composition of the SNEDDS formulations were selected from the pseudo-ternary phase diagrams. The prepared ziprasidone-SNEDDS formulations were characterized for self-emulsification time, effect of pH and robustness to dilution, droplet size analysis and zeta potential. The optimized ziprasidone-SNEDDS were used to prepare ziprasidone-SNEDDS sustained-release pellets via extrusion-spheronization method. The pellets were characterized for SEM, particle size, droplet size distribution and zeta potential. In vitro drug release studies indicated the ziprsidone-SNEDDS sustained-release pellets showed sustained release profiles with 90% released within 10?h. The ziprsidone-SNEDDS sustained-release pellets were administered to fasted and fed beagle dogs and their pharmacokinetics were compared to commercial formulation of Zeldox as a control. Pharmacokinetic studies in beagle dogs showed ziprasidone with prolonged actions and enhanced bioavailability with no food effect was achieved simultaneously in ziprsidone-SNEDDS sustained-release pellets compared with Zeldox in fed state. The results indicated a sustained release with prolonged actions of schizophrenia and bipolar disorder treatment.     

硫酸吗啡缓释片治疗100例中、重度癌痛的疗效分析

目的:探讨硫酸吗啡缓释片治疗中、重度癌痛的临床效果.方法 :选取我院住院并应用硫酸吗啡缓释片治疗的中、重度癌痛患者100例,对其临床资料进行回顾性分析,总结其VAS评分、临床疗效以及不良反应等情况.结果:患者应用硫酸吗啡缓释片控制疼痛的总有效率为92%,硫酸吗啡缓释片每12 h使用剂量从10 mg/次到300 mg/次;至首次稳定止痛平均用量为(39.25±12.60)mg/12 h;持续用药时间7~180 d,平均持续用药时间(38.56±16.22)d;不良反应发生率随用药时间延长而逐渐降低,在持续用药≥6周的68例患者中,不良反应发生率从第1周的48.5%(33/68)降低到第6周的10.3%(7/68).结论 :硫酸吗啡缓释片治疗中、重度癌痛疗效显著,且不良反应随用药时间延长而逐渐降低,是临床控制中、重度癌痛的理想选择之一.     

硫酸吗啡缓释片联合普瑞巴林治疗癌性神经病性疼痛的疗效及对患者疼痛缓解的影响

目的分析硫酸吗啡缓释片联合普瑞巴林治疗癌性神经病性疼痛的疗效及对患者疼痛缓解的影响。方法102例癌性神经病性疼痛患者,根据随机数字表法分为对照组及观察组,各51例。对照组采用硫酸吗啡缓释片治疗,观察组在对照组基础上联合普瑞巴林治疗。对比两组患者的治疗效果、疼痛程度、睡眠质量和不良反应发生情况。结果观察组治疗总有效率92.16%高于对照组的76.47%,差异具有统计学意义(P<0.05)。治疗后,两组患者的视觉模拟评分法(VAS)评分均较本组治疗前降低,且观察组降低程度优于对照组,差异均具有统计学意义(P<0.05)。两组患者的睡眠干扰(SLPD)、睡眠量(SLPQ)、睡眠充足度(SLPA)、综合睡眠障碍指数(9-items)评分均较本组治疗前改善,且观察组改善程度优于对照组,差异均具有统计学意义(P<0.05)。观察组不良反应发生率9.80%低于对照组的25.49%,差异具有统计学意义(P<0.05)。结论硫酸吗啡缓释片联合普瑞巴林治疗癌性神经病性疼痛的疗效显著,能有效缓解患者的疼痛情况,提高睡眠质量,降低不良反应发生率,安全性较高,值得应用。     

洛伐他汀缓释片的体外释放度和生物利用度

目的:考察洛伐他汀缓释片的体内外性质,评价其缓释性能.方法:测定制剂的体外释放度,考察不同因素的影响;测定制剂在比格犬体内的血药浓度,以洛伐他汀胶囊为参比制剂,计算相对生物利用度等药动学参数.结果:制剂在pH 7.0的十二烷基硫酸钠溶液中可持续释药24 h,释放规律符合零级动力学和Higuchi方程,不同的压片压力、转篮转速对药物释放有明显影响.缓释片的相对生物利用度为(111.5±16.9)%.结论:缓释片与参比制剂在吸收程度方面具有生物等效性,在吸收速度方面差异有显著性,具有良好的缓释性能.     

Influence of food on the bioavailability of a sustained-release verapamil preparation

The effects of food on the bioavailability of a sustained-release (SR) formulation of verapamil (SR-verapamil; Isoptin SR) were determined in an open, three-way single-dose study involving 12 volunteers receiving (in randomized order) the SR preparation (1 X 240 mg) either fasting or with food and a conventional formulation of verapamil (3 X 80 mg) fasting. Compared with the conventional formulation, SR-verapamil had a reduced Cmax, prolonged tmax, and unchanged t1/2, consistent with its SR formulation. The AUC was 80% of the conventional preparation. Concomitant food administration significantly prolonged the tmax of SR-verapamil from 7.3 +/- 3.4 to 11.7 +/- 6.3 h, but had little effect on Cmax, t1/2, or AUC. Similar results were obtained with the metabolite, norverapamil. Food administration also had little effect on the blood pressure and ECG effects of SR-verapamil. Cautions regarding taking this preparation with food therefore appear to be unnecessary.     

Influence of food on the oral bioavailability of moxonidine.

Moxonidine is a new centrally acting anti-hypertensive with a very low adverse drug reaction profile. Among others, the aim of the study presented here was to determine the influence of food on the pharmacokinetics of moxonidine. Single oral moxonidine doses of 0.2 mg fasting and 0.2 mg non-fasting were administered in a randomized cross-over study. Eighteen subjects participated in the study, all of whom completed the study according to the protocol. Three sets of analytical plasma data could not be evaluated pharmacokinetically giving a total number of 15 evaluable cases. Renal excretion was evaluated for all 18 subjects. Food intake had no influence on the pharmacokinetics of moxonidine. The relative bioavailability of moxonidine administered under non-fasting conditions reached 94% of the bioavailability after fasted administration. Food intake resulted in a slight decrease of Cmax and a minimal increase of tmax as compared to the fasted treatment. The absorption half-life t1/2a showed a minor prolongation. These differences were not statistically significant in any of the parameters. For t1/2 lambda 2, CLtot and Ae(24h) no statistically significant differences were found between the fasting and non-fasting treatment. The amount of moxonidine excreted unchanged in urine accounted for about 46% of the dose administered after both treatments.     

Effects of food on the bioavailability of sustained-release pinacidil in humans

The effects of a standard breakfast meal on the bioavailability of a sustained-release tablet formulation of pinacidil [(+/-)-2-cyano-1- (4-pyridyl)-3-(1,2,2-trimethylpropyl)guanidine monohydrate) were investigated in eight healthy volunteers. Concomitant food intake resulted in significantly increased maximum measured serum pinacidil concentrations, Cmax, (172 +/- 21 versus 102 +/- 49 ng/mL, p less than 0.05), and relative bioavailability, measured as AUCo-infinity (904 +/- 189 versus 697 +/- 279 ng.h/mL, p less than 0.05). The time to maximum serum concentration (tmax) was not affected by food (2.3 +/- 1.3 versus 3.3 +/- 1.2 h, p greater than 0.05), and the terminal elimination half-life, (t1/2z) was significantly decreased (4.7 +/- 2.2 versus 2.3 +/- 0.4 h, p less than 0.05).     

The effect of food on plasma and tissue concentrations of linezolid after multiple doses

In the present pilot study we investigated the effect of food ingestion on target site pharmacokinetics of linezolid, the first clinically approved oxazolidinone. For this purpose we determined free concentrations of linezolid at steady state in the interstitial space fluid of skeletal muscle and subcutaneous adipose tissue under fasting and non-fasting conditions in healthy volunteers (n = 9) by means of in vivo microdialysis. Ingestion of food led to a marked delay in the time to reach the peak concentration (T(max)), whereas the area under the concentration-time curve from 0 to 24 h (AUC(0-24 h)) remained unchanged. These data suggest that the rate of linezolid absorption is decreased by food intake. However, the overall extent of linezolid absorption and the distribution of linezolid were not affected. Tissue levels of linezolid appeared sufficiently high to eradicate pathogens with a minimum inhibitory concentration of 相似文献