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目的研究阿莫西林/克拉维酸干混悬剂和片剂与其相应参比药品的生物等效性。方法用单中心、随机、双周期、双交叉试验设计,分2个试验进行,均按体重指数分层随机均分为2组,其中阿莫西林/克拉维酸干混悬剂生物等效性试验(试验1)受试者分别服用受试药品和参比药品914 mg;阿莫西林/克拉维酸片剂生物等效性试验(试验2)受试者分别服用受试药品和参比药品1000 mg。用经过确证的HPLC法测定血清中阿莫西林和克拉维酸的浓度,按照最佳拟合法计算两种药物的药代动力学参数。结果在试验1参比药品和受试药品中,阿莫西林的t_(max)分别为(1.30±0.44),(1.32±0.52)h;C_(max)分别为(11.56±4.24),(13.41±3.94)μg·m L~(-1);t_(1/2)分别为(1.16±0.36),(1.08±0.24)h;AUC_(0-8) h分别为(31.29±7.65),(35.52±8.17)mg·h·L~(-1);AUC_(0-∞)分别为(31.87±7.80),(36.02±8.39)mg·h·L~(-1)。克拉维酸的t_(max)分别为(1.16±0.65),(1.03±0.39)h;C_(max)分别为(1.50±0.53)和(1.57±0.55)μg·m L~(-1);t_(1/2)分别为(1.08±0.48),(1.10±0.47)h;AUC_(0-8) h分别为(2.79±0.96),(3.06±0.85)mg·h·L~(-1);AUC_(0-∞)分别为(3.06±1.10),(3.52±0.94)mg·h·L~(-1)。受试药品阿莫西林和克拉维酸的相对生物利用度分别为(115.01±19.66)%,(117.78±49.44)%。在试验2参比药品和受试药品中,阿莫西林的t_(max)分别为(1.66±0.44),(1.74±0.56)h;C_(max)分别为(11.02±3.55),(10.66±2.46)μg·m L~(-1);t_(1/2)分别为(1.29±0.26),(1.33±0.31)h;AUC_(0-8) h分别为(31.52±6.89),(31.70±5.97)mg·h·L~(-1);AUC_(0-∞)分别为(33.85±8.00),(34.15±7.08)mg·h·L~(-1)。克拉维酸的t_(max)分别为(1.26±0.35),(1.14±0.35)h;C_(max)分别为(2.02±0.58),(2.08±0.61)μg·m L~(-1);t_(1/2)分别为(0.93±0.20),(0.98±0.33)h;AUC_(0-8) h分别为(3.96±1.20),(4.10±1.10)mg·h·L~(-1);AUC_(0-∞)分别为(4.20±1.23),(4.40±1.18)mg·h·L~(-1)。受试药品阿莫西林和克拉维酸的相对生物利用度分别为(102.43±15.71)%,(106.12±14.68)%。两个试验中,受试者耐受性均良好。结论阿莫西林克拉维酸干混悬剂和片剂与其相应参比药品具有生物等效性。
Objective To study the bioequivalence of amoxicillin / clavulanate dry suspensions and tablets with their corresponding reference drugs. Methods Single-center, randomized, double-cycle, double-crossover trial design was divided into two trials, which were randomly divided into two groups according to body mass index. The bioequivalence of amoxicillin / clavulanate dry suspension Test (Test 1) The subjects took 914 mg of the test drug and the reference drug, respectively; the bioequivalence test of the amoxicillin / clavulanate tablet (Test 2) took the test drug and the reference drug 1000 mg. The concentrations of amoxicillin and clavulanic acid in serum were determined by a validated HPLC method, and the pharmacokinetic parameters of the two drugs were calculated according to the best fit method. Results The t max of amoxicillin were (1.30 ± 0.44) and (1.32 ± 0.52) h respectively in the reference drug and the test drug of test 1, and the values of C max were (11.56 ± 4.24) and (13.41 (1.16 ± 0.36) and (1.08 ± 0.24) h respectively; AUC_ (0-8) h were (31.29 ± 7.65) and 35.52 ± 8.17) mg · h · L -1, and AUC 0 -∞ were (31.87 ± 7.80) and (36.02 ± 8.39) mg · h · L -1, respectively. The max values of clavulanic acid were (1.16 ± 0.65) and (1.03 ± 0.39) h, respectively; the max values of clavulanic acid were (1.50 ± 0.53) and (1.57 ± 0.55) μg · m L -1, respectively; (1.08 ± 0.48) and (1.10 ± 0.47) h respectively; AUC 0-8 h were (2.79 ± 0.96) and (3.06 ± 0.85) mg · h · L -1 ); AUC_ (0-∞) were (3.06 ± 1.10) and (3.52 ± 0.94) mg · h · L -1, respectively. The relative bioavailability of the tested drugs amoxicillin and clavulanic acid were (115.01 ± 19.66)% and (117.78 ± 49.44)%, respectively. In test 2 reference drugs and test drugs, the t_ (max) of amoxicillin were (1.66 ± 0.44) and (1.74 ± 0.56) h, respectively; C max were (11.02 ± 3.55) and (10.66 ± 2.46) μg · m L -1; t 1/2 was 1.29 ± 0.26 and 1.33 ± 0.31 h respectively; AUC 0-8 h were (31.52 ± 6.89) and (31.70 ± 5.97) mg · h · L -1; AUC_ (0-∞) were (33.85 ± 8.00) and (34.15 ± 7.08) mg · h · L -1, respectively. The max values of clavulanic acid were (1.26 ± 0.35) and (1.14 ± 0.35) h, respectively. The max values of clavulanic acid were 2.02 ± 0.58 and 2.08 ± 0.61 μg · m L -1, respectively. (0.93 ± 0.20) and (0.98 ± 0.33) h respectively; AUC_ (0-8) h were (3.96 ± 1.20) and (4.10 ± 1.10) mg · h · L -1 ); AUC_ (0-∞) were (4.20 ± 1.23) and (4.40 ± 1.18) mg · h · L -1, respectively. The relative bioavailability of the tested drugs amoxicillin and clavulanic acid were (102.43 ± 15.71)% and (106.12 ± 14.68)%, respectively. Subjects were well tolerated in both trials. Conclusions Amoxicillin clavulanate dry suspensions and tablets are bioequivalent to their corresponding reference drugs.