国产加替沙星片剂在中国男性健康受试者的临床药代动力学及生物等效性研究

目的 研究国产加替沙星片剂在健康男性志愿者中的药代动力学及生物等效性和安全性。 方法 24 名男性受试者按双交叉随机开放试验设计,每名受试者单次空腹口服国产或进口片剂400 mg,采用高效液相色谱法测定其血药浓度和尿药浓度。 结果 受试者单剂空腹口服国产和进口加替沙星片剂后体内过程均符合血管外二室模型, 平均血药高峰浓度(C_max) 分别为4.45 ± 1.04 和4.05 ±0.85 mg·L^-1, 平均达峰中位时间(T_max) 分别为0.75(0.5, 3) h 和0.75 (0.5, 2.5) h, 平均消除半衰期(T_{1 2β}) 为6.97 ±1.08 和7.19 ±0.91 h, 平均药时曲线下面积AUC_{0 ~ ∞}分别为31.99 ±3.80 和32.11 ±3.37 mg·h^-1 ·L^-1。48 h 内平均累积尿排出率分别为(79.47 ±6.00) %和(79.59 ±5.89) %。与进口片剂相比, 两制剂间的主要药代动力学参数相近, 其差异经统计学处理均无显著性, 其相对生物利用度为(99.74 ±7.42) %。 结论 受试者单剂空腹口服国产加替沙星片剂400 mg 后体内过程符合血管外二室模型, 其有效血药浓度维持时间长, 原型药物在尿中排出率高。与进口片剂具生物等效性。

Clinical pharmacokinetics and bioequivalence of domestic gatifloxacin in Chinese male volunteers

AIM: To evaluate the pharmacokinetic profiles and the bioequivalence of domestic gatifloxacin in Chinese male volunteers. METHODS: 24 healthy male volunteers received a single 400 mg dose of domestic or imported tablet of gatifloxacin in a randomized and twoway crossover design.The drug concentrations in plasma and urine were measured by HPLC method. RESULTS: The pharmacokinetics of gatifloxacin was fitted into twocompartment model after a single oral dose of 400 mg domestic and imported tablet in 24 healthy volunteers.The mean peak concentration (C_max), median peak time (T_max), elimination half-life (T_{1 2β ) and area under the curve (AUC0~∞ ) in plasma were 4.45 ±1.04 and 4.05 ±0.85 mg·L^-1, 0.75(0.5, 3) h and 0.75(0.5, 2.5) h, 6.97 ±1.08 and 7.19 ±0.91 h, 31.99 ±3.80 and 32.11±3.37 mg·h·L^-1, respectively.The cumulative urinary excretion rates within 48 h were (79.47 ± 6.00) %and (79.59 ±5.89) %.Compared with imported tablet, the differences of the main pharmacokinetic parameters were not statistically significant (P >0.05). The relative bioavailability of domestic gatifloxicin tablet was (99.74 ±7.42) %. CONCLUSION: The effective concentration maintained in plasma is longer and the cumulative urinary excretion rate is higher after a single oral dose of domestic tablet of gatifloxacin and it was equivalent to that of imported gatifloxacin.}