国产红霉素肠溶胶囊在健康志愿者的相对生物利用度

目的:研究国产红霉素肠溶胶囊与进口红霉素肠溶胶囊相对生物利用度。方法:20名健康男性志愿者双周期随机交叉口服单剂量(500 mg)国产和进口红霉素肠溶胶囊两种制剂,分别于服药前及服药后 1、2、2.5、3、3.5、4、4.5、5、6、8、10 h采集血样。用微生物法测定血清中红霉素的浓度,并对试验数据进行统计处理。结果:单次口服国产及进口红霉素肠溶胶囊的cmax分别为(2.14±0.75)和(2.11±0.77)mg/L;tmax分别为(3.10±0.58)和(3.30±0.64)h;AUC0~~10h分别为(6.63±2.08)和(6.64±2.18)mg·h/L;AUC0~∞分别为(7.38±2.34)和(7.46±2.41)mg·h/L;国产红霉素肠溶胶囊与进口品相比的相对生物利用度为(100.59± 19.47)%;用方差分析及双单侧t检验对国产和进口红霉素肠溶胶囊的生物等效性进行评价,两制剂间差异无显著性。结论:两种红霉素制剂具有生物等效性。     

氟康唑胶囊在中国健康男青年的药代动力学及生物等效性

目的：评价两种氟康唑胶囊的生物等效性。方法：以HPLC法测定18名男性健康志愿者单剂量口服两种氟康唑胶囊0.3g后血清中氟康唑浓度,3p97程序求算药动学参数。AUC0→t、AUC0→∞和Cmax对数转换后用3p97程序进行多因素方差分析及双单侧t检验判断90%可信限,tmax用非参数统计Wilcoxon法进行检验。结果：受试制剂和参比制剂的实测tmax分别为（1.8±0.8）h和（1.8±0.8）h,实测Cmax分别为（5.8±1.3）mg/L和（5.8±1.2）mg/L,t1/2分别为（33.3±4.7）h和（34.8±6.7）h,梯形法算得AUC0→t分别为（203.9±45.5）mg/（h·L）和（201.9±37.0）mg/（h·L）,AUC0→∞分别为（237.5±52.1）mg/（h·L）和（239.7±50.4）mg/（h·L）。以市售辉瑞制药有限公司产氟康唑胶囊为参比,海南益尔药业有限公司生产的氟康唑胶囊相对生物利用度F0→t为（100.8±11.1）%,F0→∞为（99.4±9.9）%。非参数统计Wilcoxon法检验结果两药tmax差异无统计学意义,AUC0→t、AUC0→∞和Cmax对数转换后用3p97程序进行多因素方差分析及双单侧t检验结果均拒绝生物不等效假设,受试制剂AUC0→t和Cmax的90%可信限分别落在参比制剂的88.8%～113.2%和86.2%～112.4%。结论：两种制剂生物等效。     

非那雄胺胶囊的人体生物等效性研究

【目的】研究国产非那雄胺胶囊与进口片剂保列治的人体生物等效性。【方法】采用LC-MS法测定18名健康男性单次交叉口服试验及对照制剂5 mg后血清中不同时间点的血药浓度,经SPSS软件统计拟合,计算其药物动力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】非那雄胺胶囊试验制剂和对照制剂的AUC0→24分别为(355.7±63.7)[ng/(h/.ml)]和(363.1±65.6)[ng/(h/.ml)],Cmax分别为(51.2±7.4)[ng/(h/.ml)]和(56.3±5.5)[ng/(h/.ml)],Tmax分别为(2.1±0.9)h和(1.9±0.4)h。【结论】试验制剂相对于对照制剂的人体生物利用度为(98.6±11.8)%,AUC0→24,Cmax经对数转换后,经以单侧t检验并计算AUC0→24,Cmax的90%可信区间分别在80%~125%,70%~143%。结果表明,两种制剂具有生物等效性。     

塞克硝唑胶囊健康人体生物等效性研究

目的研究塞克硝唑胶囊在健康志愿者中的生物等效性。方法21名男性健康志愿者随机交叉单次空腹服用试验制剂塞克硝唑胶囊和参比制剂塞克硝唑片剂。用高效液相色谱法测定血清中塞克硝唑的药物浓度。结果受试者单剂口服1000mg塞克硝唑试验药和对照药后,主要药动学参数Cmax分别为(22.69±3.60)和(23.29±3.62)mg/L;Tmax分别为(1.18±0.49)和(1.15±0.65)h;t1/2β分别为(26.43±5.77)和(27.08±5.46)h;AUC0-t分别为(701.12±123.89)和(709.93±89.06)mg·h/L;AUC0-∞分别为(761.14±147.96)和(773.71±108.23)mg·h/L。试验制剂对于参比制剂的平均相对生物利用度AUC0-∞为(98.38±12.83)%。结论受试者单剂空腹给药后塞克硝唑在体内的过程符合二室模型,AUC0-t、AUC0-∞及Cmax经统计学处理,表明试验制剂塞克硝唑胶囊和参比制剂塞克硝唑片具有生物等效性。     

埃索美拉唑肠溶胶囊人体生物等效性试验

目的采用高效液相色谱法测定受试者口服埃索美拉唑肠溶胶囊与埃索美拉唑镁肠溶片后血药浓度,评价埃索美拉唑肠溶胶囊的生物等效性。方法 2009年9月-10月,36例健康男性受试者单次交叉口服埃索美拉唑肠溶胶囊(试验制剂)和埃索美拉唑镁肠溶片(参比制剂),测定给药后不同时间点血浆中埃索美拉唑经时血药浓度,采用DAS 2.0软件进行药物代谢动力学参数计算和生物等效性评价。结果受试者单次口服试验制剂与参比制剂后,达峰时间分别为(2.19±0.96)、(2.43±0.92)h,峰浓度分别为(1 748.86±615.81)、(1 442.92±476.41)μg/L,药时曲线下面积(AUC)0-t分别为(3 927.14±1 839.10)、(3 878.79±1 734.84)μg/L.h,AUC0-∞分别为(3 998.36±1 866.22)、(3 918.31±1 773.44)μg/L.h。试验制剂与参比制剂的生物等效性为94.0%,其90%CI为(82.3%,107.2%)。结论埃索美拉唑肠溶胶囊与埃索美拉唑镁肠溶片生物等效。     

国产头孢泊肟酯胶囊人体生物等效性研究

目的 :评价国产头孢泊肟酯胶囊及进口头孢泊肟酯片剂相比较的生物等效性。方法 :采用双周期随机交叉方法进行试验设计 ,2 0名青年男性健康受试者按体重指数进行随机分层 ,分别服用 2 0 0mg国产头孢泊肟酯胶囊或进口头孢泊肟酯片剂 ,留取静脉血标本 ,以高效液相色谱法测定血药浓度 ,以 3P97程序分析计算药代动力学参数及相对生物利用度 ,判断试验药和对照药的生物等效性。结果 :试验药和对照药的平均血药峰浓度 (cmax)分别为 (3.5 2± 0 .79)mg /L和 (3.75± 0 .6 8)mg /L ,曲线下面积 (AUC)分别为 (2 0 .6 8± 4 .71)mg / (L·h)和 (2 1.18± 4 .5 5 )mg / (L·h) ,达峰时间 (tmax)分别为 (3.18± 0 .88)h和 (3.0 5± 0 .6 3)h ,血浆清除半衰期 (t1/ 2 β)分别为 (2 .4 0± 0 .5 7)h和 (2 .0 2± 0 .4 7)h。两种制剂的药时曲线吻合良好 ,所得主要药代动力学参数经统计学方法检测 ,国产胶囊的AUC1 2α置信区间 (90 % )为 87.4 %～ 10 4 .5 % ,相对生物利用度为 (98.15± 12 .5 8) %。结论 :国产的头孢泊肟酯胶囊与进口头孢泊肟酯片剂为生物等效制剂     

益智药阿尼西坦胶囊在人体内的生物等效性评价

目的:比较两种阿尼西坦胶囊在健康志愿者体内的药动学及生物等效性。方法:18名男性健康志愿受试者,采用标准二阶段交叉设计自身对照试验方法,单剂量口服阿尼西坦胶囊试验品和参比品400mg,以高效液相色谱法测定血浆中阿尼西坦主要活性代谢产物—对甲氧基苯甲酰氨基丁酸(N-anisoyl-GABA,ABA)的经时浓度,对两种阿尼西坦胶囊制剂的主要参数进行统计学比较。结果:两种阿尼西坦胶囊在健康志愿者体内的药-时曲线均符合一级吸收的单室模型,试验品和参比品的主要药动学参数达峰时间Tmax(实测值)、最大血药浓度Cmax(实测值)、曲线下面积AUC0～180min分别为:(28.90±3.23)比(30.00±6.60)min,(11.33±2.49)比(10.64±2.09)mg/L,(801.62±151.88)比(750.21±147.78)mg·min/L(F=0.1607～3.4532,P均>0.05);试验品的相对生物利用度为108.4%。结论:统计学结果显示两种阿尼西坦胶囊制剂具有生物等效性。     

盐酸伐昔洛韦在人体内的药动学和相对生物利用度

目的研究伐昔洛韦在正常人体内药动学和相对生物利用度。方法20名健康志愿者单剂量交叉口服伐昔洛韦300mg和参比片，用高效液相色谱（HPLC）法检测受试者血药浓度，并计算两者的药动学参数。结果受试药与参比药的血药浓度水平一致。其主要药动学参数t1/2分别为（3．81±0．66）h和（4．15±0．74）h；Tmax分别为（1．48±0．58）h和（1.38±0．56）h，Cmax分别为（1．86±0．50）mg／L和（2．07±0．62）mg／L，AUC分别为（7．51±1．71）mg·h／L和（7．03±0．98）mg·h／L，两制剂的药动学参数相近。用AUC估算的伐昔洛韦试验药相对生物利用度为98．0％±11．8％。结论伐昔洛韦片和参比片的AUC、Cmax经方差分析和双向单侧t检验表明两制剂生物等效；Tmax经非参数法检验表明两种制剂差异无统计学意义（P〉0.05）。     

国产环孢素胶囊在健康人体的生物等效性研究

目的:评价国产与进口环孢素胶囊的生物等效性。方法:采用随机交叉自身对照试验设计,19名健康男性志愿受试者先后单剂口服国产与进口环孢素胶囊300 mg,用HPLC法测定全血中环孢素A的浓度,以DAS1.0生物等效性评价程序处理经时血药浓度数据。结果:国产与进口环孢素A的AUC0-t分别为9045.86±1119.30μg·h·L-1和8532.17±1140.83μg·h·L-1;AUC0-∞分别为10249.03±1607.78μg·h·L-1和9373.26±1742.89μg·h·L-1;Cmax分别为1692.69±330.06μg.L-1和1645.88±292.37μg.L-1;Tmax分别为1.45±0.50h和1.33±0.43h;T1/2分别为22.20±7.81h和19.43±4.19h。以进口制剂为参比,国产环孢素胶囊的相对生物利用度为108.42±20.20%。等效性检验显示两制剂生物等效。结论:国产与进口环孢素胶囊在健康人体具有生物等效性。     

对ACL 300全自动血凝仪测定低分子肝素的评价

目的对ACL300全自动血凝仪测定低分子肝素(LMWH)进行评价,并对国产低分子肝素钙与进口参比制剂速避凝进行人体生物等效性对比.方法采用Heparin试剂盒在ACL300全自动血凝仪上测定血浆中LMWH抗Xa因子活性.结果日内精密度(变异系数,CV)均<10%,日间精密度中的高值、中值CV<10%,低值>10%(21.0%),携带污染率<0.4%,LMWH浓度在0.00 IUAXa/ml和1.0 IUAXa/ml内线性良好;国产低分子肝素钙与参比制剂的血药峰值时间(Tmax)分别为(2.97±0.53) h和(3.31±0.69) h,血药峰值浓度(Cmax)分别为(0.68±0.08)IUAXa/ml和(0.64±0.09) IUAXa/ml,曲线下面积(AUC0-t)分别为(5.38±0.79)(IUAXa/ml)·h和(5.03±0.73)(IUAXa/ml)·h.结论 ACL300全自动血凝仪测定LMWH时的精密度、携带污染率和线性良好,经生物等效性计算程序处理,相同剂量被试制剂与参比制剂为生物等效制剂.     

阿莫西林分散片与阿莫西林片的药代动力学比较研究

目的建立测定人血浆中阿莫西林浓度的RP-HPLC法,比较阿莫西林分散片与阿莫西林普通片在健康人体内药代动力学差异。方法选择12名男性健康志愿者分为2组,分别单剂量口服阿莫西林分散片与阿莫西林普通片各500 mg,采用高效液相色谱法检测阿莫西林的血药浓度。结果阿莫西林分散片与阿莫西林普通片主要药代动力学参数C_(max)分别为(742.8±68.4)μg/L和(676.7±57.2)μg/L,t_(max)分别为(2.7±0.3)h和(3 4±0.6)h,t_(1/2)分别为(4.9±1.5)h和(5.9±1.8)h,AUC_0~∞分别为(6 417.3±167.5)μg/(h·L)和(4 704.8±117.9)μg/(h·L),AUC_0~1分别为为(4 927.4±119.7)μg/(h·L)和(3436.5±103.5)μg/(h·L)。结论阿莫西林分散片t_(max)、t_(1/2)小于普通片,AUC_0~t、AUC_0~∞、C_(max)高于普通片,说明阿莫西林分散片具有一定的速释优点,明显优于普通片。     

氧氟沙星胶囊生物利用度和药物动力学的研究

目的 :考察氧氟沙星胶囊的人体相对生物利用度及药代动力学 ,生物等效性 ,从而评价其临床疗效。方法 :泰利必妥片为对照品 ,选 10名志愿受试者 ,随机分成 2组 ,自身交叉服用 ,以高效液相色谱法检测血药、尿药浓度及生物利用度 ,进而对主要动力学参数进行分析。结果 :交叉口服氧氟沙星胶囊和泰利必妥片后 2组药物动力学特性接近 ,药动学参数基本一致 ,试验药品的相对生物利用度平均为 (10 6 2 3± 5 3 6) %。结论 :氧氟沙星胶囊和泰利必妥片生物等效。     

Relative bioavailability of tizanidine 4-mg capsule and tablet formulations after a standardized high-fat meal: a single-dose, randomized, open-label, crossover study in healthy subjects

BACKGROUND: An immediate-release, multiparticulate capsule formulation of tizanidine has been developed to modify tizanidine pharmacokinetic characteristics in an attempt to decrease adverse events (AEs) while maintaining effectiveness in the management of spasticity. OBJECTIVE: This study was designed to compare the pharmacokinetic properties and tolerability of a single dose (4 mg) of an immediate-release, multiparticulate tizanidine capsule versus a commercially available tablet (reference) administered after a standardized high-fat meal. METHODS: This single-dose, randomized, open-label, 2-way crossover study in healthy, nonsmoking adult subjects was conducted at MDS Pharma Services, Belfast, United Kingdom. Subjects were randomly assigned to receive the capsule-tablet or tablet-capsule treatment. The 2 treatment periods were separated by a 6-day washout period. All treatments were administered after a standardized high-fat meal. To determine plasma tizanidine pharmacokinetic properties, blood samples were collected over 24 hours after administration. The predetermined bioequivalence range for the test drug (capsule) was 80% to 125% of the reference drug (tablet). Drug tolerability was assessed using routine physical examination, including vital-sign measurements; laboratory analysis (hematology, biochemistry, and urinalysis); 12-lead electrocardiography; direct observation; spontaneous reporting; and non specific questioning. RESULTS: This study included 18 subjects (12 men, 6 women; mean [SD] age, 26 [7] years). The mean height and body weight of the subjects were 176 (8) cm and 70.1 (9.6) kg, respectively. The peak exposure, as measured by mean natural logarithm-transformed C(max) values, was significantly lower with the capsule compared with the tablet (2.7 vs 4.0 ng/mL; P < 0.019), and mean TmaX was significantly longer (2.6 vs 1.2 hours; P < 0.001). The 90% CIs for the capsule:tablet treatment ratios were 70.55 to 121.94 for AUC(0-lat) and 70.12 to 118.75 for AUC(0-infinity). The capsule did not achieve the protocol-defined definition of bioequivalence when given after a high-fat meal. All AEs were transient and mild in intensity, with asthenia being the most common event with the capsule and tablet formulations, occurring in 5 (28%) and 8 (44%) subjects, respectively. CONCLUSIONS: In this small study in healthy volunteers, after a single oral dose was administered following a high-fat meal, the mean C(max) was significantly lower and mean T(max) was significantly longer with the capsule formulation of tizanidine compared with the tablet. The capsule formulation was found not to be bioequivalent to the tablet when given with food. Based on these findings, caution is needed when a patient is switched between the capsule and tablet formulations of tizanidine, or when the timing of administration of either formulation is changed in relation to food ingestion.     

Comparison of the pharmacokinetics of lansoprazole 15- and 30-mg sachets for suspension versus intact capsules

OBJECTIVE: The pharmacokinetic profiles of single doses of lansoprazole 15- and 30-mg sachets for suspension were compared with those of corresponding doses of lansoprazole oral capsules. METHODS: Healthy adult male and female subjects were randomized (1:1 ratio) into 2 Phase 1, open-label, single-dose, 2-sequence, 2-period complete crossover studies. In the first study, each subject received 1 lansoprazole 15-mg sachet mixed with water and 1 lansoprazole 15-mg oral capsule; in the second study, each subject received 1 lansoprazole 30-mg sachet mixed with water and 1 lansoprazole 30-mg oral capsule. Administration of the 2 formulations was separated by a washout period of > or =7 days. Blood samples were collected before and after each administration to assess the pharmacokinetic parameters of lansoprazole and bioequivalence between suspension and capsule. RESULTS: Thirty-six subjects (19 males, 17 females) with a mean (SD) age of 32.0 (9.6) years and mean (SD) body weight of 68.6 (10.5) kg received lansoprazole 15 mg. Thirty-six subjects (22 males, 14 females) with a mean (SD) age of 38.0 (8.3) years and mean (SD) body weight of 75.1 (9.7) kg received lansoprazole 30 mg. The pharmacokinetic parameters of the 15- and 30-mg lansoprazole sachets for suspension were similar to those of the corresponding doses of the oral capsules. The mean (SD) values for C(max) and AUC from time 0 to infinity (AUC(0-infinity) for the lansoprazole 15-mg sachet (591.9 [242.3] ng/mL and 1614 [2065] ng.h/mL, respectively) did not differ significantly from those for the lansoprazole 15-mg capsules (578.6 [275.2] ng/mL and 1620 [2290] ng.h/mL, respectively). These parameters also did not differ significantly between the lansoprazole 30-mg sachet and 30-mg capsule: mean (SD) C(max), 1103 (428.3) and 1077 (465.6) ng/mL, respectively; mean (SD) AUC(0-infinity), 2655 (1338) and 2669 (1311) ng.h/mL, respectively. The 90% Cls for C(max) and AUC(0-infinity) ratios were contained within the 0.80 to 1.25 equivalence range, supporting bioequivalence. CONCLUSIONS: These findings suggest that the 15- and 30-mg lansoprazole sachets for suspension are bioequivalent to the corresponding doses of oral capsules. The sachet for suspension may provide an alternative route of administration to patients who have difficulty swallowing solid oral formulations.     

盐酸西替利嗪的人体药代动力学研究

目的 :用进口盐酸西替利嗪片 (A)为对照品 ,评价片剂B的相对生物利用度和生物等效。方法 :采用随机交叉分组试验设计 ,10名健康成年男性受试者分别口服单剂量 2 0mg测试品和对照品 ,采用HPLC法测定人血清中药物浓度进行生物等效性的研究。结果 :对照品和测试品的tmax分别为 ( 1 72± 0 39)h和 ( 1 6 5± 0 55)h ,Cmax分别为 ( 6 13± 12 1 7)ng/ml和 ( 597± 119 8)ng/ml,AUC0～ 2 4分别为 ( 2 855 1± 52 8 3)h·ng/ml和 ( 30 16 4± 70 2 8)h·ng/ml,t1/2分别为 ( 11 5± 2 7)h和 ( 12 0±2 9)h ;片剂B相对A的平均生物利用度为 ( 10 0 2± 7 4 ) %。结论 :测试片剂B与对照片剂A具生物等效性     

麻敏维C缓释胶囊人体生物等效性研究

目的评价麻敏维C缓释胶囊（每粒含盐酸伪麻黄碱90mg和马来酸氯苯那敏4mg）在人体的生物等效性。方法于2006年6月采用随机交叉自身前后对照试验设计,26例受试者分别单次和多次空腹口服麻敏维C缓释胶囊（试验制剂）和复方盐酸伪麻黄碱缓释胶囊（参比制剂）,与不同时间点取血样,采用液-质联用（HPLC/MS）法测定人血浆中盐酸伪麻黄碱和马来酸氯苯那敏的浓度,以DAS软件计算药物代谢动力学参数,并进行生物等效性评价。结果单次给药后,两组分的主要药物代谢动力学参数无统计学意义（P〉0.05）。试验制剂中马来酸氯苯那敏和盐酸伪麻黄碱生物利用度分别为104.31%和109.19%。多次给药后,两组分的主要药物代谢动力学参数无统计学意义（P〉0.05）。试验制剂的马来酸氯苯那敏和盐酸伪麻黄碱的生物利用度分别为103.58%和99.37%。结论麻敏维C缓释胶囊和复方盐酸伪麻黄碱缓释胶囊具有生物等效性。     

A randomized, open-label, two-period, crossover bioavailability study of two oral formulations of tacrolimus in healthy Korean adults

BACKGROUND: Tacrolimus is a macrolide immunosuppressant used in transplantation. It has been shown to have a comparable therapeutic effect and a low adverse drug reaction profile relative to cyclosporme. OBJECTIVE: The present study compared the pharmacokinetics of twice-daily doses of 2 tacrolimus formulations used in clinical practice in Korea: a conventional (reference) formulation and a more recently developed (test) formulation. The bioavailability of the 2 formulations was evaluated based on the requirement of 20% deviation at a power of 80%. METHODS: This study had a randomized, open-label, 2-period, crossover, non-inferiority design. There was a 96-hour treatment period for each formulation, with a 3-week washout period between formulations. Each healthy adult subject received two 1-mg capsules of the reference or test formulation of tacrolimus twice daily (morning and evening), for a total daily dose of 4 mg. Blood samples were obtained during the 96-hour period after the first dose in each treatment period, with tolerability assessments performed up to 2 weeks after the first dose in each period. The primary pharmacokinetic parameters were C(max) and AUC from time 0 to the last measured concentration and extrapolated to infinity. Secondary pharmacokinetic parameters were T(max), t(1/2), C(min0-24), AUC(0-24), and C(96). RESULTS: The study enrolled 29 healthy Korean volunteers (22 men, 7 women; mean [SD] age, 29 [7] years; age range, 20-51 years; mean weight, 66 [10] kg; mean height, [171 17] cm). All volunteers completed both treatment periods. The 90% Cls for the ratios of the pharmacokinetic parameters (test:reference drug) were 119.25-161.29 for C(max), 95.29-129.04 for AUC(0-t), and 95.63-131.42 for AUC(0-infinity). Based on the 80% to 125% bioequivalence criterion, these results indicated that pharmacokinetic exposure to the test drug was not inferior to that of the reference drug. Both formulations were well tolerated, with no serious adverse events reported. CONCLUSION: In these healthy Korean adults, there were no statistically significant differences between the pharmacokinetic parameters of the more recently developed oral formulation of tacrolimus and the conventional formulation.     

Bioavailability and pharmacokinetic comparison between generic and branded azithromycin capsule: a randomized, double-blind, 2-way crossover in healthy male Thai volunteers

BACKGROUND: Azithromycin is a semisynthetic azalide antibiotic with extensive tissue penetration and a prolonged t(12). It is used once daily for 3 days in the treatment of a number of bacterial infections. However, based on a literature search, information concerning its pharmacokinetic properties, including the relative bioavailability of a newly developed generic capsule formulation compared with an established branded one in the Thai population, has not been reported. OBJECTIVE: The aim of this study was to compare the relative bioavailability and other pharmacokinetic properties of a newly developed generic capsule formulation of azithromycin with those of an established branded formulation in healthy male volunteers in Thailand. METHODS: A randomized, double-blind, 2-way crossover study was performed in healthy male Thai volunteers under fasting conditions with a washout of 30 days between the study periods. A single dose of 2 x 250-mg azithromycin capsules was orally administered, and blood samples were collected over a period of 120 hours. Plasma azithromycin concentrations were determined using a validated high-performance liquid chromatography method with fluorescence detection after derivatization with 9-fluorenylmethyloxycarbonyl chloride. A plasma concentration-time curve was generated for each volunteer from which the C(max), T(max), AUC(0-Iast), AUC(0-infinity), t(1/2), and kappa(e) were determined using noncompartmental analysis. Bioequivalence was defined using regulatory requirements set forth by Thailand, Association of Southeast Asian Nations, and the US Food and Drug Administration (bioequivalence acceptance range, 0.80-1.25). RESULTS: A total of 14 volunteers completed the study. The mean age of volunteers was 20.8 years (range, 19-23 years), and the mean body weight was 62.8 kg (range, 50.6-70.0 kg). The mean (SD) T(max), C(max), AUC(0-last), and AUC(0-infinity) values after administration of the generic and branded formulations were 1.46 (0.41) versus 1.54 (0.41) hours, 425.23 (208.45) versus 431.75 (198.16) ng/mL, 3919.77 (1549.65) versus 4344.79 (1654.98) ng . h/mL, and 4027.05 (1839.13) versus 4515.53 (2203.87) ng . h/mL, respectively. The relative bioavailability of the generic and branded formulations were 1.00 (0.17). The mean (SD) t1/2 values after administration of the generic and branded formulations were 26.43 (10.92) and 28.10 (13.13) hours, respectively. The analysis of variance results of the natural logarithm (In) -transformed values found no significant effect of formulation, period, or sequence on the studied pharmacokinetic parameters. The 90% CIs of the treatment ratios for the Intransformed values of C(max), AUC(0-last), and AUC(0-infinity) were 0.82 to 1.11, 0.91 to 1.06, and 0.91 to 1.08, respectively. All were within the standard bioequivalence acceptance range of 0.80 to 1.25. No adverse events were reported in this study. CONCLUSIONS: In this small study in a selected population of healthy male Thai volunteers, the C(max) and AUC were not statistically significantly different between generic and branded formulations of a single, 2 x 250-mg dose of azithromycin capsules. The generic and branded formulations were found to be bioequivalent. Both formulations were well tolerated.     

Development and validation of limited-sampling strategies for predicting amoxicillin pharmacokinetic and pharmacodynamic parameters

Amoxicillin plasma concentrations (n = 1,152) obtained from 48 healthy subjects in two bioequivalence studies were used to develop limited-sampling strategy (LSS) models for estimating the area under the concentration-time curve (AUC), the maximum concentration of drug in plasma (C(max)), and the time interval of concentration above MIC susceptibility breakpoints in plasma (T>MIC). Each subject received 500-mg amoxicillin, as reference and test capsules or suspensions, and plasma concentrations were measured by a validated microbiological assay. Linear regression analysis and a "jack-knife" procedure revealed that three-point LSS models accurately estimated (R(2), 0.92; precision, <5.8%) the AUC from 0 h to infinity (AUC(0-infinity)) of amoxicillin for the four formulations tested. Validation tests indicated that a three-point LSS model (1, 2, and 5 h) developed for the reference capsule formulation predicts the following accurately (R(2), 0.94 to 0.99): (i) the individual AUC(0-infinity) for the test capsule formulation in the same subjects, (ii) the individual AUC(0-infinity) for both reference and test suspensions in 24 other subjects, and (iii) the average AUC(0-infinity) following single oral doses (250 to 1,000 mg) of various amoxicillin formulations in 11 previously published studies. A linear regression equation was derived, using the same sampling time points of the LSS model for the AUC(0-infinity), but using different coefficients and intercept, for estimating C(max). Bioequivalence assessments based on LSS-derived AUC(0-infinity)'s and C(max)'s provided results similar to those obtained using the original values for these parameters. Finally, two-point LSS models (R(2) = 0.86 to 0.95) were developed for T>MICs of 0.25 or 2.0 microg/ml, which are representative of microorganisms susceptible and resistant to amoxicillin.