二甲双胍缓释片人体药代动力学及其相对生物利用度

目的 研究国产盐酸二甲双胍缓释片在人体药代动力学行为并与普通片进行等效性评价比较,并估算其药代动力学参数。方法 20名受试者分两组交叉服用缓释片和普通片,用RP-HPLC法测定血浆中药物浓度,并估算相应的药动学参数。结果 单剂量口服1000mg缓释片和普通片后估算的AUC_0-24分别为11.95±2.62μg·h^-1·ml^-1和10.72±2.23μg·h^-1·ml^-1;C_max分别为1.50±0.22μg·ml^-1和2.34±0.30μg·ml^-1;T_max分别为3.38±0.8h和1.61±0.32h;t_1/2分别为4.94±0.47h和3.20±0.38h;多剂量1000mg·d^-1时AUC_ss分别为15.04±3.01μg·h^-1·ml^-1和14.51±2.69μg·h^-1·ml^-1;C_max分别为1.68±0.25μg·ml^-1和1.60±0.26μg·ml^-1;C_min分别为0.15±0.03μg·ml^-1和0.12±0.04μg·ml^-1;Cav分别为0.62±0.13μg·ml^-1和0.61±0.11μg·ml^-1;T_max分别为3.61±0.60h和1.88±0.38h;AUC_0-24和AUC_ss经对数转换后方差分析和双单侧t检验，显示两制剂吸收程度生物等效。结论受试制剂和参比制剂吸收程度生物等效，但具有缓释特性。盐酸二甲双胍缓释片的相对生物利用度单剂量时为（111.5±8.3）%，多剂量时为（103.6±9.2）%。     

普罗布考包合物胶囊在家犬体内的药代动力学与相对生物利用度

目的研究普罗布考包合物胶囊在家犬体内的药代动力学与相对生物利用度。方法用高效液相色谱法测定6条健康犬po 250 mg普罗布考片(制剂A)或普罗布考包合物胶囊(制剂B)后不同时间血浆中活性药物的浓度,绘制药-时曲线,计算药代动力学参数及相对生物利用度。结果制剂A和制剂B的药-时曲线符合二室模型,其T_max均为(9.3±2.1) h,C_max分别为(1.5±1.0) μg·mL^-1和(2.3±0.9) μg·mL^-1,AUC_0～240分别为(85±56) μg·h·mL^-1和(134±55) μg·h·mL^-1。以制剂A为参比,制剂B中普罗布考的相对生物利用度为(198±90)%,两种制剂的AUC_0～240有显著性差异(P<0.05)。结论初步分析认为,改善普罗布考的水溶性是提高普罗布考生物利用度的关键因素之一。     

HPLC法测定国产洛索洛芬钠片人体相对生物利用度

目的 建立人血浆中洛索洛芬钠浓度的HPLC测定方法,研究健康受试者口服国产洛索洛芬钠片的药代动力学,以进口洛索洛芬钠片作为参比制剂,计算两制剂的相对生物利用度,判断两种制剂是否等效。方法 血浆样品加入内标后经三氯乙酸沉淀蛋白、涡旋、离心,吸取上清液进样。色谱柱为Shimadzu VP-ODS(150mm×4.6mm i.d.,5μm C₁₈),流动相为0.05mol·L^-1磷酸二氢钾-甲醇(27∶73)(v/v),紫外检测波长230nm。测定了20名受试者单剂量口服两种洛索洛芬钠片60mg后血药浓度时间过程。结果 最低检测浓度0.2μg·ml^-1,回收率大于80%,日间和日内的变异系数小于10.5%,线性范围为0.2～12.0μg·ml^-1(r=0.9998),符合生物样品分析的要求。主要药动学参数分别为:国产洛索洛芬钠片:t_1/2为1.39±0.15h,AUC_0-6h 10.71±1.45μg·h·ml^-1,C_max7.23±1.02μg·ml^-1,t_max0.4±0.1h；参比制剂t_1/2为1.41±0.15h,AUC_0-6h 10.46±1.32μg·h·ml^-1,C_max7.49±1.26μg·ml^-1,t_max0.4±0.1h。结论 建立的HPLC法简单快速，定量可靠准确，适合于洛索洛芬钠临床研究。洛索洛芬钠受试制剂的相对生物利用度为（103.2±15.1）%。经统计学分析，两制剂生物等效。     

普卢利沙星片的健康人体药动学

目的 健康志愿受试者口服普卢利沙星片后,测定血浆中其活性代谢物(UFX)并作药动学研究。方法 10名受试者分别单剂量和多剂量稳态时服用普卢利沙星片(相当于200 mg UFX),采集血浆和尿液样品,液相色谱分离荧光检测UFX浓度,3P97软件计算药动学参数。结果 单剂量时测得UFX的主要药动学参数分别为c_max(1.64±0.29)μg·ml^-1,t_max(0.7±0.2)h,AUC_0-36(6.87±1.78)h·μg·ml^-1,AUC_0-∞(7.14±1.79)h·μg·ml^-1,t_1/2(7.54±0.59)h,MRT(8.76±0.65)h;0～36 h尿液累积排泄量为(56.85±9.12)%。稳态时测得UFX的主要药动学参数分别为c_max(1.26±0.41)μg·ml^-1,t_max(0.8±0.3)h,AUC_0-36(7.77±2.73)h·μg·ml^-1,AUC_0-∞(8.10±2.70)h·μg·ml^-1,t_1/2(7.71±1.13)h,MRT(9.85±1.40)h。结论 健康志愿受试者口服普卢利沙星片后,在体内转化为活性代谢物(UFX)发挥作用,主要经尿液排泄。每日2次,每次2片(相当于200mg UFX),在体内无积蓄。男女健康受试者的主要药动学参数无显著性差异。     

两种国产格列齐特片人体生物利用度的研究

目的 比较两种格列齐特片的生物等效性。方法 用HPLC法测定血浆中格列齐特浓度,研究8名受试者口服两种国产片剂的药动学和生物利用度,并用方差分析和双单侧检验及90%可信限考察生物等效性。结果 8名受试者口服单剂量格列齐特片的药动学参数,试验品的t_max3.38±0.52h,C_max19.91±3.61μg·ml^-1,t_1/26.52±2.40h,AUC 278.86±94.74μg·h·ml^-1;对照品的t_max3.38±0.52h,C_max17.59±3.13μg·ml^-1,t_1/27.77±3.34h,AUC 300.94±87.49μg·h·ml^-1,相对生物利用度为92.46±10.47%。结论 两种片剂经统计分析,C_max的90%可信区间在79.1～99.6%,AUC的可信区间在105.8%～107.4%,这两种片剂完全生物等效。     

LC-MS/MS法测定人血浆中辛伐他汀的浓度及相对生物利用度

目的 建立人体血浆中辛伐他汀的LC-MS/MS测定方法,研究辛伐他汀片在男性健康志愿者体内的药代动力学行为,评价其生物利用度和生物等效性。方法 20名健康成年男性志愿者采用随机分组自身交叉对照试验设计,单剂量口服辛伐他汀片40 mg后,用LC-MS/MS联用法测定血浆中药物浓度。结果 试验制剂和参比制剂的主要药代动力学参数:t_max分别为(1.8±1.3)h和(2.10±1.00)h;c_max分别为(7.12±1.61)μg·L^-1和(7.38±1.54)μg·L^-1;AUC_(0-24)分别为(30.50±11.25)μg·L^-1·h^-1和(30.17±10.21)μg·L^-1·h^-1;t_1/2分别为(3.90±0.78)h和(3.76±0.85)h。以AUC_(0-24)计算的试验制剂的相对生物利用度为101.2%±7.8%。结论 建立的分析方法准确灵敏,测得的数据可靠,统计学分析表明两种制剂生物等效。     

HPLC/MS研究国产盐酸班布特罗片及其代谢物特布他林人体生物等效性

目的研究国产班布特罗片剂和进口片剂进行人体生物等效性研究。方法20名健康受试者随机交叉给药,用液相色谱/质谱联用测定血浆中班布特罗其代谢物特布他林的浓度。结果经数据处理,单次口服国产和进口班布特罗片剂后班布特罗的药代动力学参数:AUC_0-t分别为(52±21)μg·h·L^-1和(51±20)μg·h·L^-1,T_max分别为(2.9±0.9)h和(2.6±0.7)h,C_max分别为(6.0±2.6)μg·L^-1和(6.2±2.9)μg·L^-1。特布他林:AUC_0-t分别为(191±30)μg·h·L^-1和(197±37)μg·h·L^-1,T_max分别为(4.2±1.0)h和(4.2±1.0)h,C_max分别为(10±5)μg·L^-1和(10±4)μg·L^-1。国产班布特罗片剂单次给药后的相对生物利用度为102%±8%(班布特罗),100%±12%(特布他林)。结论经统计学证明两制剂有生物等效性。     

替硝唑胶囊健康人体内的药动学与生物等效性研究

目的 研究替硝唑胶囊在健康人体内的相对生物利用度和生物等效性。方法 20名健康成年男性志愿者,采用随机分组自身交叉对照试验,单剂量口服1.0 g替硝唑胶囊后,用高效液相色谱法测定血浆中药物浓度。结果 替硝唑线性范围为0.208～41.6μg·ml^-1;平均回收率98.64%～99.56%,日内和日间精密度(RSD)均小于10.0%。试验制剂和参比制剂的主要药代动力学参数:T_max:(1.6±0.9)和(1.6±0.9)h;C_max:(18.03±2.35)和(18.45±2.78)μg·ml^-1;AUC_(0-60):(394.39±60.32)和(390.29±53.20)mg·L^-1·h;AUC_(0-∞):(435.20±77.15)和(426.36±66.88)mg·L^-1·h;T_1/2:(17.43±2.47)和(16.73±2.25)h。以AUC_(0-60)计算的受试制剂的相对生物利用度为(101.1±7.7)%。结论 两种制剂生物等效。     

伏立康唑胶囊人体药动学及相对生物利用度研究

目的 研究健康受试者口服伏立康唑胶囊的药动学和相对生物利用度。方法 20名健康受试者随机服用伏立康唑受试胶囊剂和参比片剂各100 mg,用HPLC-MS/MS测定血浆中伏立康唑的浓度。结果 主要药动学参数,伏立康唑受试制剂与参比制剂的T_max分别为(0.75±0.15)和(0.84±0.25)h,C_max分别为(605.4±136.6)和(595.2±134.7)ng·mL^-1;t_1/2分别为(4.91±1.44)和(5.06±2.06)h,AUC_0-15分别为(1737.6±325.1)和(1750.6±352.8)ng·h·mL^-1。受试制剂与参比制剂的AUC_0-15和C_max经双单侧t检验,T_max经非参数检验,差异均无统计学意义。结论 统计学结果表明,2种制剂生物等效。     

固相萃取结合HPLC-MS测定人血浆中奥曲肽的浓度及相对生物利用度固相萃取结合HPLC-MS测定人血浆中奥曲肽的浓度及相对生物利用度

目的建立人血浆中奥曲肽浓度的HPLC-MS测定法，研究国产奥曲肽注射剂的人体生物利用度。方法 血浆样品用HPL 1cc固相萃取小柱萃取，经Waters Xetrra C₁₈ MS分离后测定。18名健康志愿受试者采用随机交叉试验设计，分别im奥曲肽试验制剂和参比制剂200 μg，不同时间点采血，比较两者的生物利用度。结果线性范围0.5～40 μg·L^-1，方法回收率为97.1%～100.5%。日内、日间RSD分别为1.1%～1.6%，2.9%～4.8%。单剂量im奥曲肽200 μg后两种制剂的C_max分别为（19±10） μg·L^-1和（19±11） μg·L^-1，t_max分别为（0.50±0.15） h和（0.52±0.20） h；AUC_0～7h分别为（50±25） h·μg·L^-1和（50±25） h·μg·L^-1，t_1/2分别为(1.5±0.8) h 和(1.5±0.8) h。二者之间均无显著性差异，以进口奥曲肽为参比制剂，国产奥曲肽注射液的相对生物利用度为101%±10%。结论该方法灵敏、准确度高，可用于奥曲肽体内过程研究。两注射剂为生物等效性制剂。     

Formulation and in vitro/in vivo investigation of carbamazepine controlled-release matrix tablets

Carbamazepine controlled-release tablet formulations containing hydroxypropyl methylcellulose (HPMC) as matrix material at different concentrations were developed and evaluated in vitro and in vivo. The formulation containing 10% HPMC (HPMC-10) showed a controlled-release profile comparable to that of a commercially available, controlled-release carbamazepine preparation (Tegretol CR 200). The kinetics of controlled-release carbamazepine tablets was examined in eight healthy volunteers. The peak plasma concentration of 1.99 +/- 0.56 micrograms.ml-1 was obtained for HPMC-10 at 15.0 +/- 9.0 h, and 1.33 +/- 0.35 micrograms.ml-1 for Tegretol CR 200 at 15.2 +/- 8.9 h, and AUC0-infinity values of 85.2 +/- 30.8 micrograms.h.ml-1 and 76.9 +/- 20.7 micrograms.h.ml-1, respectively. Developed formulation (HPMC-10) was found to be bioequivalent to Tegretol CR 200 and, controlled release was obtained with smoother concentration-time curve resulting in less fluctuations.     

Single dose absorption profiles and bioavailability of two different salbutamol tablets

In a single dose cross-over experiment in twelve healthy adults a comparison of the absorption profiles and the relative bioavailability was made between a new salbutamol containing tablet (preparation A = Salbutax) and a commercially available and accepted formulation as reference (preparation B), both containing 4 mg salbutamol. Salbutamol plasma concentrations were measured frequently during a period of 16 h post dosing. Maximum salbutamol plasma concentrations after intake of product A and product B on an empty stomach were reached after 2.3 +/- 0.9 (= mean +/- S.D.) and 2.4 +/- 1.1 h, respectively, and accounted for 14.3 +/- 2.5 and 12.8 +/- 2.6 micrograms X l-1, respectively. The differences were not found to be significant (p greater than 0.05). The areas under the plasma concentration-time curves (AUC0----16), as obtained after administration of tablet A and tablet B, accounted for 73.5 +/- 14.0 and 65.0 +/- 11.8 micrograms X l-1 X h, respectively, the difference being marginally significant (p = 0.05). This results in a relative bioavailability of 114.3 +/- 15.7% for the product A 4-mg tablets. It is concluded that both products can be considered as having comparable bioavailability.     

北京产硫酸吗啡控释片的人体相对生物利用度研究

目的·· :研究正常人单剂量口服北京产硫酸吗啡控释片的人体相对生物利用度 ,及多次给药的稳态血药浓度和波动性。方法·· :正常健康志愿者19例,随机自身交叉口服北京产硫酸吗啡控释片和进口片30mg;晚期癌痛病人27例次 ,随机(部分病人自身交叉)多次口服北京产硫酸吗啡控释片和进口片至稳态。采用GC -MS测定血药浓度。结果··:求得北京产硫酸吗啡控释片和进口片的Cmax 为14.65ng·ml-1±s3.08ng·ml-1 和14.71ng·ml-1±s2.13ng·ml -1,Tmax 为3.84h±s0.50h和3.84h±s0.37h,曲线下面积AUC为76.67ng·h·ml -1±s8.32ng·h·ml-1 和80.06ng·h·ml-1±s10.89ng·h·ml-1,北京产硫酸吗啡控释片的相对生物利用度为96.89%±s15.33 % ;达稳态时谷浓度分别为15.11ng·ml -1±s8.98ng·ml -1和12.52ng·ml -1±s10.14ng·ml -1 ,峰浓度分别为24.06ng·ml -1±s11.18ng·ml -1和20.32ng·ml -1±s13.18ng·ml -1,血药浓度的波动系数( %)为47.96±s19.91和46.89±s18.77。结论··:北京产硫酸吗啡控释片的人体相对生物利用度符合要求 ,多次给药的稳态血药浓度和波动性与进口片无显著性差异。     

Comparative bioavailability of tetracycline and lymecycline

The relative bioavailability of lymecycline and tetracycline hydrochloride was compared in 12 healthy volunteers in a double-blind cross-over study using a high performance liquid chromatographic method for plasma and urine analyses. A statistical significant difference in favour of tetracycline hydrochloride was found concerning the mean AUC and the mean lag time. The relative bioavailability of lymecycline was only 70% compared with tetracycline in multiple dosing (19.13 +/- 5.39 micrograms ml-1 h and 27.22 +/- 6.26 micrograms ml-1 h respectively) and 80% in a single dose (21.88 +/- 4.23 micrograms ml-1 h and 26.91 +/- 6.01 respectively) and the mean lag time of tetracycline was only 60% compared with lymecycline.     

Multiple dose comparison of a whole 240 mg verapamil sustained-release tablet with two half tablets

Twelve healthy male volunteers were studied in a balanced crossover comparison of an intact 240 mg verapamil sustained-release tablet (Securon SR, Isoptin Forte Retard) given once daily for 7 days, and the same dose given as two half tablets. One subject was withdrawn because of asymptomatic second degree heart block on day 3 of verapamil treatment. The mean Cmax after dosing with whole tablets, 143 (95 per cent confidence limits 91.6-223) ng ml-1 was lower than after dosing with half tablets, 160 (107-241) ng ml-1, but this was not significant (p = 0.49). The mean steady-state Cmin values after whole and half tablets were also similar: 22.2 (12.6-39.4) ng ml-1 and 22.0 (16.2-29.9) ng ml-1, respectively (p = 0.96). The mean (+/- S.D.) tmax, AUC0-24 and t 1/2 were not significantly different: whole tablet 3.5 +/- 1.2 h, 1733 +/- 1125 ng.h ml-1 and 10.5 +/- 3.4 h, respectively, and half tablets 3.6 +/- 1.0 h, 1780 +/- 1057 ng.h ml-1 and 9.6 +/- 2.3 h, respectively. The findings for plasma norverapamil were generally similar to those for the parent drug. This investigation indicates that the formulation is sufficiently robust to retain its sustained-release properties when the tablet is halved.     

氯化钾泡腾片人体相对生物利用度研究

目的　探讨内源性药物人体药代动力学及相对生物利用度研究方法。方法　18名健康志愿者按随机三交叉设计进行试验。在研究的3周期中,两周期分别po氯化钾泡腾片或氯化钾普通片剂2g,另一周期不服药作对照,用以排除非药物性钾的影响。每一周期在给药后收集0 - 2 ,2 - 4,4-6 ,6 - 8,8- 10 ,10 - 12 ,12 - 2 4,2 4- 48h尿样,测定尿钾量。用带一级吸收的一室模型拟合尿钾累积排泄量时间数据。以给药后0 - 48h尿钾累积排泄量计算生物利用度,用方差分析和双单侧t检验进行制剂的等效性分析。结果　氯化钾泡腾片的药代动力学参数为T_1/2ke=(6±5 )h ,T_1/2ka=(0.08±0.08)h ,ku=(0.09±0.04)h^-1,X_max/f=(18±8)mmol;氯化钾普通片的药代动力学参数为T_1/2ke=(8±5 )h ,T_1/2ka=(0.11±0.11)h ,k_u=(0.07±0.04)h^-1 ,X_max/f=(18±8)mmol。氯化钾泡腾片相对生物利用度F=97.5 %±15.2%。结论　氯化钾泡腾片和氯化钾普通片剂有生物等效性。     

Bioavailability of morphine after administration of a new bioadhesive buccal tablet

A new bioadhesive buccal morphine tablet was developed for controlled release delivery of drug and improved bioavailability compared with oral controlled release tablet. In order to characterize the pharmacokinetic properties of this bioadhesive buccal formulation, a bioavailability study was performed in 12 healthy volunteers who received: a 30 mg oral controlled release tablet (A); a 20 mg aqueous solution retained in the mouth for 10 min (B); and the 60 mg bioadhesive buccal tablet placed between the lower gum and lip for 6 h (C). The mean amount of morphine absorbed from the solution was very low, only 2 mg of the 20 mg dose. After administration of forms A and C, plasma levels exhibit typical sustained release concentration–time curves. The mean amount of drug recovered from the residual bioadhesive buccal tablet after 6 h indicated that approximately 50% of the dose was released from the bioadhesive buccal tablet. The relative bioavailability of the buccal tablet (corrected for residual unabsorbed dose) compared with the controlled-release tablet was 98% based on the morphine AUC values. Good correlations between the AUC and the C_max of the bioadhesive tablet for the drug and metabolite plotted versus the amount of morphine absorbed were found. © 1998 John Wiley & Sons, Ltd.     

Studies of mefloquine bioavailability and kinetics using a stable isotope technique: a comparison of Thai patients with falciparum malaria and healthy Caucasian volunteers.

1 A mefloquine hydrochloride tablet (250 mg base equivalent to 4.8 +/- 0.6 mg kg-1; mean +/- s.d.) and deuterium labelled mefloquine hydrochloride solution (250 mg base) were given to six adult male Thai patients with acute falciparum malaria and six healthy Swiss adult male volunteers (equivalent to 3.5 +/- 0.1 mg kg-1). 2 The relative bioavailability of the tablet formulation derived from comparison of the areas under the plasma concentration-time curves was similar in both groups; 87 +/- 11% and 89 +/- 10% (mean +/- s.d.). 3 The rate of drug absorption appeared to be similar in the two groups but peak plasma mefloquine concentrations were approximately three times higher in the Thai patients (1004 +/- 276 ng ml-1 for the tablet and 1085 +/- 280 ng ml-1 for the suspension) compared with the Swiss volunteers (319 +/- 73 ng ml-1 for the tablet, and 369 +/- 121 ng ml-1 for the suspension). 4 Estimates of the oral clearance CLpo of unlabelled mefloquine were significantly lower (17.5 +/- 4.4 ml h-1 kg-1) in the Thai patients compared with 28.8 +/- 3.5 ml h-1 kg-1 in the Swiss volunteers; P less than 0.05). Terminal elimination half-lives were significantly shorter in the patients (10.3 +/- 2.5 days) than in the volunteers (16.7 +/- 1.9 days; P less than 0.005). Differences of a similar magnitude were observed when comparing the pharmacokinetic parameters derived from the deuteromefloquine plasma concentrations. 5 Both genetic and disease related factors are likely to account for the large pharmacokinetic differences between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oral absorption profile of nitrendipine in healthy subjects: a kinetic and dynamic study.

1. In nine healthy male subjects the kinetics of nitrendipine were assessed after i.v. administration and its absorption profile was studied when given by a tablet formulation and by an osmotic pumping device (Osmet) with a zero-order in vitro release of 2.62 +/- 0.19 mg h-1 for 13 h. 2. Plasma concentrations of nitrendipine and its pyridine metabolite, heart rate and blood pressure were determined at regular intervals after drug administration. 3. After i.v. nitrendipine, the plasma concentration declined triexponentially with a mean terminal elimination half-life of 11.7 +/- 5.4 h. The mean systemic plasma clearance was 1.47 +/- 0.22 l min-1. 4. Administration of the Osmet resulted in a relatively smooth plasma concentration-time profile in comparison with the tablet. The mean plateau concentration was 2.63 +/- 1.31 ng ml-1 and the duration of this plateau was 10.7 +/- 3.2 h. The intake of food gave rise to a transient increase of the plasma concentration of both nitrendipine and its pyridine metabolite. 5. The mean bioavailability of nitrendipine from the Osmet (8.2 +/- 1.6%) was lower than from the tablet (11.1 +/- 4.5%), which is probably due to release of nitrendipine in lower parts of the G.I. tract where absorption is not or less possible. 6. Intravenous administration caused a transient decrease in DBP of 26 +/- 4%, accompanied by a maximal reflex tachycardia of 46 +/- 17%. No clear haemodynamic effects were observed after oral administration. The Osmet produced less side-effects (headache) than the tablet.