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地夫可特为前体药物,口服给药后迅速吸收并代谢为活性产物21-羟基地夫可特(21-OH DFZ)。本文研究健康中国受试者单次和多次口服地夫可特片后21-OH DFZ的药代动力学特征。12名健康受试者,男女各半,按3×3拉丁方设计分别餐后单次交叉口服地夫可特片6、12和24 mg,两次服药间的清洗期为1周。三周期单次给药结束后,经过1周清洗期进行多次给药试验,每日一次餐后口服地夫可特片12 mg,连续服药7天。受试者餐后单次口服地夫可特片6、12和24 mg后21-OH DFZ的Cmax分别为(37.7±11.6)、(61.5±17.7)和(123±23)ng·mL-1,t1/2分别为(1.90±0.32)、(1.96±0.27)和(2.13±0.34)h,AUC0-14 h分别为(96.6±25.9)、(190±44)和(422±107)ng·h·mL-1。多次给药达稳态后,21-OH DFZ的稳态平均血药浓度Cav为(7.00±1.66)ng·mL-1,稳态血药浓度波动度DF为7.7±1.2。结果表明,口服地夫可特片6~24 mg剂量内,21-OH DFZ在健康受试者体内呈线性药动学特征,药动学特征不存在性别差异,多次给药后药物在体内无蓄积。
Docetaxel is a prodrug that is rapidly absorbed and metabolized to the active product 21-OH-DRF (21-OH DFZ) after oral administration. In this paper, pharmacokinetic characteristics of 21-OH DFZ after single and multiple oral doses of defocus tablets in healthy Chinese subjects were studied. Twelve healthy subjects, half male and half female, were dosed 6,12 and 24 mg of delfo tablets at a single crossover meal at 3 x 3 Latin squares, with a washout interval of 1 week between doses. Three cycles after a single administration, after a week of washing for multiple administration trials, once daily oral meal Epoca Tablets 12 mg, continuous medication for 7 days. The Cmax of 21-OH DFZ after single oral picofutil tablets 6, 12 and 24 mg after meal were (37.7 ± 11.6), (61.5 ± 17.7) and (123 ± 23) ng · mL -1, respectively (1.90 ± 0.32), (1.96 ± 0.27) and (2.13 ± 0.34) h respectively, and the AUC0-14 h were (96.6 ± 25.9), (190 ± 44) and (422 ± 107) ng · h · mL-1. After multiple administrations reached the steady state, the steady-state mean plasma concentration of 21-OH DFZ Cav was (7.00 ± 1.66) ng · mL-1, and the steady-state plasma concentration fluctuation DF was 7.7 ± 1.2. The results showed that 21-OH DFZ in the dose of 6 ~ 24 mg was linear pharmacokinetic characteristics in healthy volunteers, there was no gender difference in the pharmacokinetic characteristics. After multiple doses, the drug was in vivo No accumulation.