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目的通过对健康受试者口服不同剂量盐酸米诺环素缓释片后的药动学研究,探讨其在中国人体内的药动学特征,并以普通片为对照制剂,比较研究缓释片的缓释行为,为临床用药提供依据。方法 12名中国健康志愿者采用多剂量单序列给药设计方案,进行低、中、高(45,90,135 mg)3剂量组单次给药和中剂量组多次给药试验,并进行普通片(100 mg)的单剂量和多剂量试验。采用高效液相色谱-质谱(HPLC-MS)测定血药浓度。结果盐酸米诺环素缓释片低、中、高3剂量组单次给药后的主要药动学参数如下:ρmax分别为(0.477 0±0.128 0)、(1.011±0.191)、(1.500±0.281)μg·mL-1,t max分别为(3.3±1.1)、(3.6±0.8)、(3.4±0.7)h,t1/2分别为(17.1±5.4)、(18.3±4.9)、(17.9±3.4)h,AUC0-t分别为(9.391±3.019)、(20.01±3.07)、(31.81±6.80)μg·h·mL-1;中剂量组多次给药的主要药动学参数为:ρav为(0.844 0±0.225 0)μg·mL-1,DF为(1.1±0.2),ρssmax为(1.438±0.383)μg·mL-1,t max为(3.5±0.8)h,t1/2为(19.3±4.4)h,AUC0-t为(31.18±9.39)μg·h·mL-1;普通盐酸米诺环素片100 mg单次给药的主要药动学参数如下:ρmax为(1.418±0.427)μg·mL-1,t max为(2.6±0.7)h,t1/2为(16.9±3.9)h,AUC0-t为(25.35±5.80)μg·h·mL-1;普通盐酸米诺环素片100 mg多次给药的主要药动学参数如下:ρav为(1.229±0.377)μg·mL-1,DF为(1.3±0.2),ρmax为(2.188±0.652)μg·mL-1,t max为(2.3±0.7)h,t1/2为(17.7±2.4)h,AUC0-t为(44.83±16.29)μg·h·mL-1。结论受试者单次口服45、90、135 mg盐酸米诺环素缓释片后,血浆中米诺环素的ρmax和AUC0-t随给药剂量的增大而增大,呈现线性药动学特征;无性别差异。多次给药研究发现,在相同给药间隔内米诺环素在健康受试者体内的暴露量增加约50%。与普通片比较发现,盐酸米诺环素缓释片具有明显的缓释特征。
Objective To study the pharmacokinetics of minocycline hydrochloride tablets in healthy volunteers after oral administration of different doses of minocycline hydrochloride, and to explore its pharmacokinetic characteristics in Chinese human body. Compare with conventional sustained-release tablets Sustained release behavior, provide the basis for clinical medication. Methods Twelve Chinese healthy volunteers were given single or multiple doses of low, middle and high dose (45, 90 and 135 mg) single dose and multiple dose of medium dosage group (100 mg) single and multiple dose trials. Plasma concentration was determined by high performance liquid chromatography-mass spectrometry (HPLC-MS). Results The main pharmacokinetic parameters of the minocycline hydrochloride low dose, middle dose and high dose three groups were as follows: ρmax were (0.477 ± 0.128 0), (1.011 ± 0.191), (1.500 ± T were (3.3 ± 1.1), (3.6 ± 0.8), (3.4 ± 0.7) h and (17.1 ± 5.4), (18.9 ± 4.9) and ± 3.4) h and AUC0-t were (9.391 ± 3.019), (20.01 ± 3.07) and (31.81 ± 6.80) μg · h · mL-1, respectively. The main pharmacokinetic parameters of multiple dose of middle dose group were: ρav was (0.844 ± 0.225 0) μg · mL-1, DF was (1.1 ± 0.2), ρssmax was (1.438 ± 0.383) μg · mL-1, t max was (3.5 ± 0.8) (19.3 ± 4.4) h, and AUC0-t was (31.18 ± 9.39) μg · h · mL-1. The main pharmacokinetic parameters of single-dose administration of minocycline hydrochloride 100 mg were as follows: ρmax was (1.418 ± 0.427) μg · mL-1, tmax was (2.6 ± 0.7) h, t1 / 2 was (16.9 ± 3.9) h and AUC0-t was (25.35 ± 5.80) μg · h · mL- The main pharmacokinetic parameters of cyclosporin 100 mg multiple administration were as follows: ρav was (1.229 ± 0.377) μg · mL-1, DF was (1.3 ± 0.2) and ρmax was (2.188 ± 0.652) μg · mL-1 , t max was (2.3 ± 0.7) h, t1 / 2 was (17.7 ± 2.4) h, and AUC0-t was (44.83 ± 16.29) μg · h · mL-1. Conclusions After a single oral administration of 45, 90, 135 mg minocycline hydrochloride sustained release tablets, the ρmax and AUC0-t of minocycline in plasma increased with increasing dose, presenting linear pharmacokinetics Academic characteristics; no gender differences. Multiple dose studies found that minocycline exposure in healthy subjects increased by about 50% over the same dosing interval. Compared with ordinary tablets, minocycline hydrochloride sustained-release tablets have obvious sustained-release characteristics.