Pharmacokinetics and bioequivalence study of ranitidine film tablets in healthy male subjects

The aim of the present study was to compare the bioavailability of ranitidine (CAS 66357-35-5) from two different ranitidine hydrochloride (CAS 66357-59-3) film tablets (Ranitab 150 mg film tablets as test preparation and 150 mg film tablets of the originator product as reference preparation). The study was conducted according to an open-label, randomised two-period cross-over design with a wash-out phase of 9 days. Blood samples for pharmacokinetic profiling were taken up to 24 h post-dose, and ranitidine plasma concentrations were determined with a validated HPLC method with UV-detection. Maximum plasma concentrations (Cmax) of 461.8 ng/ml (test) and 450.6 ng/ ml (reference) were achieved. Areas under the plasma concentration-time curve (AUC (0-infinity) of 2,488.6 ng . h/ml (test) and 2,528.8 ng . h/ml (reference) were calculated. The median tmax was 2.83 h (test) and 3.04 h (reference). Plasma elimination half-lives (t1/2) of 2.78 h (test) and 2.89 h (reference) were determined. Both primary target parameters AUC(0-infinity) and Cmax were tested parametrically by analysis of variance (ANOVA) and the 90% confidence intervals were between 91.93 %-106.98 % (AUC (0-infinity) and 92.34%-118.85% (Cmax). Bioequivalence between test and reference preparation was demonstrated since for both parameters AUC and Cmax the 90 % confidence intervals of the T/R ratios of logarithmically transformed data were in the generally accepted range of 80 %-125 %.     

Bioequivalence study of two brands of meloxicam tablets in healthy human Pakistani male subjects

Meloxicam is a cyclooxygenase-2, preferential inhibitor non-steroidal anti-inflammatory drug (NSAID) and belongs to an enolic acid (oxicam) class used for the treatment of osteoarthritis and rheumatoid arthritis. The purpose of this single dose randomized cross-over study was to assess bioequivalence of two brands of oral meloxicam tablets (Xobix manufactured by Hilton Pharma (Pvt.) Ltd. as a reference and tablet Melfax by AGP (Pvt.) Ltd. as a test) in 18 healthy male volunteers in local population of Pakistan. The data obtained were subjected to non-compartment model pharmacokinetic analysis. The value of C(max) calculated in present study was 1.051 +/- 3.762 microg/mL for reference formulation and 1.023 +/- 4.102 microg/mL (the mean +/- SEM) for test sample. The value of T(max) was 3.125 +/- 1.004 h for reference standard and 3.750 +/- 1.469 h (the mean +/- SEM) for test sample. The area under the curve from zero to infinity (AUC(0-72)) was 28.667 +/- 0.414 microg x h/mL for reference standard and 28.367 +/- 0.333 microg x h/mL for test sample (the mean +/- SEM). The t1/2 values were 13.694 +/- 0.568 h and 13.319 +/- 0.567 h (the mean +/- SEM) for reference formulation and for test sample, respectively. The test formulation was found to be bioequivalent to reference formulation based on the pharmacokinetic parameters.     

塞克硝唑片在健康人体的药动学及生物等效性

目的:研究塞克硝唑片在人体的药动学特点和生物等效性。方法:20名健康男性受试者,采用双周期交叉、自身对照试验设计,单剂量口服塞克硝唑受试制剂和参比制剂(沙巴克)2.0g,采用反相高效液相色谱法测定其血药浓度,计算其药动学参数和相对生物利用度,评价两种制剂的生物等效性。结果:塞克硝唑受试制剂和参比制剂的主要药动学参数:t1/2分别为(27.1±4.2)h和(26.6±4.7)h;tmax分别为(2.3±1.1)h和(2.9±1.1)h;Cmax分别为(49.6±6.4)mg.L-1和(46.2±4.2)mg.L-1;AUC0-96分别为(1 832.0±180.2)mg.L-1.h和(1 847.1±204.1)mg.L-1.h;AUC0-∞分别为(2 022.4±205.7)mg.L-1.h和(2 042.3±264.0)mg.L-1.h。方差分析结果表明,两种制剂的主要药动学参数之间差异无显著性。塞克硝唑受试制剂的相对生物利用度为(99.99±11.92)%。结论:经统计学分析,两种制剂具有生物等效性。     

美洛昔康分散片在健康人体内的药代动力学和生物等效性研究

目的研究美洛昔康分散片在24名健康志愿者体内的药代动力学和生物等效性。方法采用两制剂双周期交叉试验设计,单剂量口服15mg的美洛昔康受试制剂或参比制剂,用高效液相色谱法测定血浆中美洛昔康药物浓度。结果美洛昔康在0.015～3μg/ml范围内线性良好(r=0.9996),平均回收率89.43%～103.17%,日内和日间精密度(RSD)均<6.00%。试验制剂和参比制剂的t1/2分别为(22±7)和(22±7)h,Cmax分别为(1.32±0.27)和(1.42±0.32)μg/ml,Tmax分别为(4.6±1.1)和(4.8±1.9)h;AUC0～96分别为(42±14)和(45±14)mg·L-1·h-1;AUC0～∞分别为(45±17)和(48±18)mg·L-1·h-1。受试制剂对参比制剂的相对生物利用度为(93±10)%。两者的lnAUC、lnCmax经方差分析和双单侧检验证明差异无统计学意义(P>0.05),两制剂的Tmax经非参数法检验差异无统计学意义(P>0.05)。结论美洛昔康分散片和参比制剂具有生物等效性。     

Pharmacokinetics and bioequivalence study of doxycycline capsules in healthy male subjects

The aim of the present study was to compare the bioavailability of doxycycline (CAS 564-25-0) from two different doxycycline hyclate (CAS 24390-14-5) capsules (Monodoks 100 mg capsule as test preparation and 100 mg capsule of the originator product as reference preparation) in 24 healthy male subjects. The study was conducted according to an open-label, randomised two-period cross-over design with a wash-out phase of 16 days. Blood samples for pharmacokinetic profiling were taken up to 72 h post-dose, and doxycycline plasma concentrations were determined with a validated HPLC method with UV-detection. Maximum plasma concentrations (Cmax) of 1,715.1 ng/ml (test) and 1,613.3 ng/ml (reference) were achieved. Areas under the plasma concentration-time curve (AUC(0-infinity)) of 28,586.5 ng x h/ml (test) and 29,047.5 ng x h/ml (reference) were calculated. The median tmax was 1.88 h (test) and 2.00 h (reference). Plasma elimination half-lives (t1/2) of 16.49 h (test) and 16.75 h (reference) were determined. Both primary target parameters AUC(0-infinity) and Cmax were tested parametrically by analysis of variance (ANOVA) and the 92.39 %-103.53% (AUC(0-infinity)) and 98.45%-111.74% (Cmax). Bioequivalence between test and reference preparation was demonstrated since for both parameters AUC and Cmax the 90% confidence intervals of the T/R ratios of logarithmically transformed data were in the generally accepted range of 80 0%-125%.     

Pharmacokinetic and bioequivalence testing of atorvastatin formulations in healthy male volunteers

The aim of this study was to compare the bioavailability of two atorvastatin formulations (Divator Drogsan Pharmaceuticals, Ankara, Turkey, as the test formulation, and Lipitor, Pfizer Ireland Pharmaceuticals, Dublin, Ireland, as the reference formulation) in 52 healthy volunteers. The study was conducted using a randomised, single-dose, two-way crossover study with a 2-week washout period between the doses. Since the 90% confidence intervals for Cmax, AUC0-72 and AUC0-proprtional to ratios for both, the parent atorvastatin and its main active metabolite ortho-hydroxy atorvastatin, were within the pre-defined Bioequivalance acceptance limits approved by EMEA, we concluded that the atorvastatin formulation elaborated by Drogsan Pharmaceuticals, was bioequivalent to the Lipitor in its rate and extent of absorption.     

Lack of bioequivalence between two aciclovir tablets in healthy subjects

OBJECTIVE: This study aimed to compare the systemic bioavailability of two aciclovir tablets, Rouz-Aciclovir (test) and Zovirax (reference), in 12 healthy volunteers. METHODS: In a crossover design, each subject received a single oral dose of aciclovir 400 mg followed by a 7-day washout period. Plasma concentrations of aciclovir were measured for up to 12 hours using a validated high-performance liquid chromatography method with a lower limit of quantification of 50 microg/L. RESULTS: The mean values of maximum plasma concentration (C(max)), time to C(max) (t(max)), area under the plasma concentration-time curve from time 0 to 12 hours (AUC(12)) and from time 0 to infinity (AUC(infinity)), and plasma half-life following administration of the test product were 999.6 microg/L, 2.08 h, 4911.2 microg/L . h, 5417.7 microg/L . h and 3.08 h, respectively, and for the reference product 775.8 microg/L, 2.58 h, 3862.1 microg/L . h, 4295.4 microg/L . h and 3.14 h, respectively. The test/reference geometric ratio for C(max) (90% CI) was 1.30 (97.1, 174.8). The test/reference geometric ratios for AUC(12) (90% CI) and AUC(infinity) (90% CI) were 1.26 (99.7, 159.1) and 1.24 (98.9, 155.6), respectively. Therefore, the 90% CIs of C(max), AUC(12) and AUC(infinity) were not within the acceptable range of 80 and 125 suggested by the US FDA bioequivalence guideline. CONCLUSION: The results of the present study suggest that the aciclovir test product was not bioequivalent to the reference product. The exact reasons for this remain to be determined. However, we think the difference should be attributed to the difference in the type and amounts of ingredients used in the formulation that probably affect the contact time of aciclovir with the sites of absorption in the gut.     

依折麦布片在中国健康受试者中的药代动力学和生物等效性研究

目的研究空腹及餐后条件下单剂量依折麦布片的药代动力学特征,评价其生物等效性和安全性。方法空腹组和餐后组各入组48例健康受试者,采用单中心、单剂量、空腹/餐后、随机、开放、两制剂、两周期、双交叉的试验设计,每周期受试者单次空腹或餐后口服受试药物或参比药物依折麦布片10 mg,用HPLC-MS/MS法测定给药后不同时间点受试者血浆中依折麦布和总依折麦布(依折麦布+依折麦布-葡萄糖醛酸结合物)的浓度。采用非房室模型计算药代动力学参数,评价2种依折麦布的生物等效性。结果单次空腹给药受试药物与参比药物血浆中总依折麦布的主要药代动力学参数:C_max分别为(70.74±30.08)和(72.32±25.46)ng·mL^-1;t_max分别为1.12和1.25 h;t_1/2分别为(14.02±7.40)和(13.75±6.88)h;AUC_0-t分别为(530.93±221.48)和(514.81±215.49)h·ng·mL^-1;AUC_0-∞分别为(565.54±227.79)和(550.86±239.24)h·ng·mL^-1。单次餐后给药受试药物与参比药物血浆中总依折麦布的主要药代动力学参数:C_max分别为(109.78±49.31)和(112.33±40.73)ng·mL^-1;t_max分别为2.00和1.50 h;t1/2分别为(15.50±8.76)和(13.36±6.61)h;AUC_0-t分别为(627.51±267.46)和(565.57±188.63)h·ng·mL^-1;AUC_0-∞分别为(683.91±316.10)和(616.88±218.22)h·ng·mL^-1。受试药物和参比药物的主要药代动力学参数C_max、AUC_0-t、AUC_0-∞经对数转换后进行方差分析,在90%置信区间范围内,空腹状态下总依折麦布分别为88.90%~103.31%,97.84%~109.29%,96.66%~109.94%;餐后状态下总依折麦布分别为84.79%~103.87%,102.71%~112.92%,103.35%~115.71%。结论空腹和餐后状态下,健康受试者口服两种依折麦布的主要药代动力学参数相近,且安全性良好,具有生物等效性。     

氨酚伪麻美芬片Ⅱ在健康人体内的药动学和生物等效性

目的研究2种国产氨酚伪麻美芬片Ⅱ在健康人体内的药动学及生物等效性。方法20名健康男性受试者按2制剂双周期交叉试验设计口服受试制剂和参比制剂各2片,采用高效液相色谱-紫外法测定血浆中对乙酰氨基酚的浓度,高效液相色谱-质谱联用法测定血浆中伪麻黄碱和右啡烷的浓度,使用DAS软件计算药动学参数并进行生物等效性统计分析。结果参比制剂和受试制剂中对乙酰氨基酚的c_(max)分别为(6 600±s 1200),(7600±2100)μg·L~(-1);t_(max)分别为(1.1±0.6),(0.9±0.6)h;A4 UC_(0～16)分别为(27 900±4700),(28 700±4 400)μg·h·L~(-1);t(1/2)分别为(4.0±1.0),(4.2±1.4)h;伪麻黄碱的C_(max)分别为(213±33),(222±34)μg·L~(-1);t_(max)分别为(1.8±0.5),(1.6±0.6)h;AUC_(0～24)分别为(1 676±261),(1 659±282)μg·h·L~(-1);t_(1/2)分别为(4.6±0.5),(4.6±0.5)h;右啡烷的c_(max)分别为(7±4),(7.5±2.9)μg·L~(-1);t_(max)分别为(2.1±0.6),(1.9±0.7)h;AUC_(0～24)分别为(38±15),(39±12)μg·h·L~(-1);t_(1/2)分别为(6±3),(5.1±2.7)h。以AUC_(0～t)计算,受试制剂中对乙酰氡基酚、伪麻黄碱和右美沙芬的相对生物利用度分别为(103±8)%,(100±18)%,(109±27)%,2种制剂的主要药动学参数经统计学检验,差异无显著意义(P>0.05)。结论2种制剂具有生物等效性。     

Average bioequivalence of generic clarithromycin tablets in healthy Thai male volunteers

The objective of this study was to assess bioequivalence of 500-mg clarithromycin tablets in 24 healthy volunteers. In a randomized, single dose, fasting state, two-period, crossover study design with a 1-week washout period, each subject received a 500-mg clarithromycin tablet. Plasma samples were collected over a 24-h period after administration and were analyzed by using a validated method using high performance liquid chromatography (HPLC) with electrochemical detection. The time to reach the maximal concentration (t(max),h), the peak concentration (C(max),ng/ml) and the area under the curve (AUC(0- infinity),ng h/ml) of the Reference and Test formulations were 2.1+/-0.7 vs 2.1+/-0.7, 2474+/-702 vs 2559+/-744 and 15803+/-6120 vs 17683+/-6650, respectively. Relative bioavailability was 1.12. The 90% confidence interval (90% CI) of C(max) and AUC(0- infinity) were 95.6-110.8% and 3.5-122.0%, respectively. Bioequivalence between the test and reference preparation can be concluded.     

Pharmacokinetic interaction between tadalafil and bosentan in healthy male subjects

Tadalafil, an oral phosphodiesterase 5 (PDE5) inhibitor, is being investigated as a treatment for pulmonary arterial hypertension. Bosentan is an oral endothelin receptor antagonist widely used in the treatment of pulmonary arterial hypertension. Tadalafil is mainly metabolized by cytochrome P450 (CYP) 3A4, and as bosentan induces CYP2C9 and CYP3A4, a pharmacokinetic interaction is possible between these agents. This open-label, randomized study investigated whether any pharmacokinetic interaction exists between tadalafil and bosentan. Healthy adult men (n = 15; 19-52 years of age) received 10 consecutive days of tadalafil 40 mg once daily, bosentan 125 mg twice daily, and a combination of both in a 3-period, crossover design. Following 10 days of multiple-dose coadministration of bosentan and tadalafil, compared with tadalafil alone, tadalafil geometric mean ratios (90% confidence interval [CI]) for AUCtau and Cmax were 0.59 (0.55, 0.62) and 0.73 (0.68, 0.79), respectively, with no observed change in tmax. Following coadministration of bosentan with tadalafil, bosentan ratios (90% CI) for AUCtau and Cmax were 1.13 (1.02, 1.24) and 1.20 (1.05, 1.36), respectively. Tadalafil alone and combined with bosentan was generally well tolerated. In conclusion, after 10 days of coadministration, bosentan decreased tadalafil exposure by 41.5% with minimal and clinically irrelevant differences (<20%) in bosentan exposure.     

恩替卡韦分散片的健康人体相对生物利用度及生物等效性研究

目的:以中美上海施贵宝制药有限公司生产的恩替卡韦片(博路定)为参比制剂,研究江苏正大天晴药业股份有限公司研制的恩替卡韦分散片受试制剂的相对生物利用度,以判断两种制剂是否具有生物等效性。方法:采用随机双交叉试验设计,20例男性健康受试者禁食过夜后空腹单剂量口服恩替卡韦0.5mg,液相色谱-串联质谱法(LC-MS/MS)测定血浆中恩替卡韦的浓度,应用药物与统计(DrugAndStatistics,DAS)程序计算有关药动学参数并评价两种制剂的生物等效性。结果:单剂量口服受试制剂和参比制剂的主要药动学参数Cmax分别为(5.15±1.35)和(4.55±2.46)ng.mL-1;Tmax分别为(0.44±0.20)和(0.75±0.31)h;t1/2分别为(147±127)和(127±48)h;AUC0～96分别为(13.7±2.6)和(13.0±1.9)ng.h.mL-1;AUC0～∞分别为(27.2±13.8)和(23.3±4.5)ng.h.mL-1;相对生物利用度为(107.5±24.7)%。两制剂的AUC0～96无显著性差异,Cmax和Tmax有显著性差异。结论:两制剂吸收程度等效;与参比制剂比较,受试制剂...     

Pharmacokinetic and bioequivalence study of etoricoxib tablet in healthy Bangladeshi volunteers

The aim of this study was to compare the pharmacokinetic properties of two etoricoxib (CAS 202409-33-4) 60 mg formulations, namely Etocox-60 (test product) and reference product, and to evaluate whether these two formulations meet the FDA criteria to assume bioequivalence. Twenty-four healthy volunteers were enrolled into this randomized, single-dose, 2-way crossover, open-label pharmacokinetic study. Subjects were randomly assigned to receive the test formulation followed by the reference formulation or vice versa as a single dose of 60 mg tablets after 12 h overnight fasting, with a washout period of two weeks. Following oral administration, blood samples were collected at 0 (baseline), 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0, and 120.0 h. Serum concentration of etoricoxib was assessed using a high performance liquid chromatographic-UV spectrometry procedure. The pharmacokinetic parameters were determined by the non-compartmental method. After administering a single dose of 60 mg of each etoricoxib formulation, the obtained mean (SD) values for the test and reference products were 1.26 (0.33) and 1.29 (0.35) microg/ml for Cmax; 3.25 (2.64) and 2.63 (1.40) h for t(max); 29.63 (8.31) and 30.40 (5.85) h x microg/ml for AUC0-120; and 31.84 (10.97) and 33.00 (8.10) h x microg/ml for AUC0-infinity, respectively. The mean t1/2 was found 27.99 (7.87) h and 29.84 (7.93) h for test and reference product respectively. From paired t-test, no significant differences were observed (p > 0.05) for any pharmacokinetic parameters. After analysis of variance, no period, sequence or formulation effects were observed for any pharmacokinetic property. The 90% confidence intervals of the test/reference mean ratios of the 1n-transformed AUC0-120, AUC0-infinity and Cmax mean values were 95.90% (85.37%-107.74 %), 94.69% (84.43%-106.20%) and 97.87% (85.54 %-111.98 %), respectively, which fell within the predetermined FDA bioequivalence range of 80%-125%. This single-dose study found that the test and reference formulations of etoricoxib met the regulatory criteria for bioequivalence in terms of both rate and extent of absorption.     

辛伐他汀片及其活性代谢产物在中国健康人体的药动学和生物等效性评价

目的:研究辛伐他汀片及其活性代谢物辛伐他汀酸在健康人体内的药动学特征和生物等效性评价。方法:24名健康受试者随机交叉、单剂量口服40 mg参比和试验辛伐他汀片后;采用LC-MS/MS测定血浆中辛伐他汀和辛伐他汀酸的浓度;应用DAS2.1.1软件计算药动学参数,并进行生物等效性评价。结果:参比和试验制剂辛伐他汀的主要药动学参数如下:Cmax分别为(6.8±4.0)μg·L-1和(6.9±4.5)μg·L-1;tmax分别为(2.4±1.9)h和(2.2±1.5)h;t1/2分别为(5.0±2.6)h和(6.3±6.7)h;AUC0-24分别为(38.1±27.0)μg·h·L-1和(36.5±24.2)μg·h·L-1;AUC0-∞分别为(40.7±29.3)μg·h·L-1和(41.8±28.7)μg·h·L-1。参比和试验制剂辛伐他汀酸的主要药动学参数如下:Cmax分别为(3.8±1.7)μg·L-1和(3.8±1.6)μg·L-1;tmax分别为(4.3±1.6)h和(4.2±1.0)h;t1/2分别为(5.8±3.2)h和(7.3±6.9)h;AUC0-24分别为(30.1±11.1)μg·h·L-1和(30.0±10.5)μg·h·L-1;AUC0-∞分别为(34.0±14.4)μg·h·L-1和(35.6±17.4)μg·h·L-1。以AUC0-24计算辛伐他汀和辛伐他汀酸的相对生物利用度分别为(105.7±55.6)%和(106.5±42.8)%。结论:经方差分析及双单侧t检验结果显示,辛伐他汀与辛伐他汀酸的试验制剂和参比制剂在人体内生物等效。     

Pharmacokinetic model of R-roscovitine and its metabolite in healthy male subjects

OBJECTIVE: To characterize the pharmacokinetics of R-roscovitine, a novel cyclin-dependent kinase inhibitor, and its carboxylate metabolite in man. METHOD: Twelve healthy male subjects received single oral doses of 50, 100, 200, 400 or 800 mg in a hierarchical 3-period, 6-sequence crossover design. One dose was given after breakfast, the others under fasting conditions. R-roscovitine and the carboxylate metabolite were measured in plasma and urine. A 2-compartment model for R-roscovitine with 1 compartment for the metabolite and a component for first-pass extraction was adequate. Protein binding was calculated from plasma and urine data. RESULTS: R-roscovitine undergoes nonsaturatable first-pass extraction, rapid metabolism, exhibits high nonsaturated protein binding, is slowly absorbed from the GI tract and is rapidly and extensively distributed into tissues. The slow release of the molecule from tissue determines the apparent terminal half-life. Food delays the absorption and slows down the absorption rate but does not influence bioavailability. The formation rate of the carboxylate is a determinant of the plasma concentrations of this metabolite. It has low protein binding, limited tissue distribution and a renal clearance reflecting with good water solubility. CONCLUSION: The compartmental analysis clarified important pharmacokinetic aspects relevant for the clinical development of the compound.     

Comparative bioequivalence study of leflunomide tablets in Indian healthy volunteers

The pharmacokinetics of teriflunomide [CAS No. 163451-81-8], the metabolite of leflunomide [CAS No. 75706-12-6] has been evaluated in adult human volunteers after oral administration of tablet formulation. However, no published data is available regarding the bioavailability of this in the Indian population. In light of the above, a study was designed to carry out a bioequivalence study of 2 preparations of leflunomide 20 mg in healthy Indian male volunteers.24 healthy male volunteers (age, 25±4.1 years; weight, 57.58±7.01 kg) were enrolled in this study. Each subject received a test and reference formulation in a single dose, fasting 2 period, 2 way crossover study with a wash out period of 4 weeks. Analysis of teriflunomide from plasma samples was done by a simple and sensitive HPLC method using UV detection developed in our laboratory. An analysis of variance was performed on the pharmacokinetic parameters Cmax, AUC0-t, AUC0-∞ using GLM procedures in which sources of variation were subject, formulation, and period.The results indicated that there are no statistically significant differences between the 2 products in either the mean concentration-time profiles or in the obtained pharmacokinetic parameters. 90% confidence limits for the log transformed data of Cmax, AUC0-t, AUC0-∞. were within the acceptable range of 0.80-1.25.The results indicate that the 2 products are bioequivalent in terms of rate and extent of drug absorption. Both the preparations were well tolerated with no adverse reactions throughout the study.     

健康人体内替硝唑片的药代动力学及生物等效性研究

目的研究替硝唑片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试验设计,单剂量口服1.0g替硝唑片后,用高效液相色谱法测定血浆中药物浓度。结果替硝唑在0.208～41.6μg/ml浓度范围内线性良好(r=0.99975),平均回收率98.6%～99.6%,日内和日间标准误(sx)均<10.0%。替硝唑试验制剂和参比制剂的主要药代动力学参数:峰时(Tmax)(:1.5±0.8)和(1.5±1.3)h;峰浓度(Cmax):(20±3)和(21±3)μg/ml;曲线下面积(AUC)0￣60h:(390±55)和(391±48)mg·L-1·h;AUC0￣∞:(427±79)和(424±59)mg·L-1·h;T1/2:(16.6±2.8)和(16.1±1.9)h,以AUC0￣60h计算的受体制剂的相对生物利用度为(100±6)%。结论建立的分析方法准确灵敏,统计学分析表明两种制剂生物等效。     

五酯胶囊对拉米夫定人体内药物动力学的影响

目的研究五酯胶囊对拉米夫定片的人体药动学是否具有影响,为临床合理用药提供参考。方法12名健康受试者,男女各半,按男女分层后随机分为2组,按双周期交叉口服五酯胶囊和空白胶囊,剂量(2粒.次-1,3次.d-1),共服7 d,并于第7 d同时服拉米夫定片(100 mg),洗脱期为15 d。采用HPLC法测定血药浓度,计算药动学参数并进行方差分析,比较两周期的药动学参数差异。结果健康受试者拉米夫定单次给药药动学参数:tmax为(0.83±0.36)h,Cmax为(1 458.2±350.4)ng.mL-1,AUC0~16为(4 310.2±911.7)ng.h.mL-1,t1/2为(2.59±0.54)h,CL/F为(23.7±4.8)L.h-1。合用五酯胶囊后拉米夫定的药动学参数:tmax为(0.6±0.2)h,Cmax为(1 508.3±449.1)ng.mL-1,AUC0~16为(3 941.5±811.0)ng.h.mL-1,t1/2为(2.4±0.5)h,CL/F为(25.4±5.0)L.h-1,tmax具有显著性差异。结论五酯胶囊能加快拉米夫定的吸收。