国产注射用盐酸米诺环素人体药动学研究

Pharmacokinetics of minocycline hydrochloride for injection in healthy human

目的研究国产注射用盐酸米诺环素人体内的药动学特征,为临床提供合理给药方案。方法12名健康志愿者随机分成3组,采用3×3的交叉设计,每人单剂量分别静脉给予100、200和300m g注射用盐酸米诺环素,2h衡速滴完,分别在给药前和给药后0、0.25、0.5、0.75、1、1.5、2、4、6、8、12、24、48、72h取血。每次间隔一周。采用高效液相色谱法测定血清中米诺环素浓度。结果用3P 97程序计算其药动学参数。单次静脉注射盐酸米诺环素100、200和300m g,药动学参数cm ax分别为(3.11±0.67)μg/m l、(7.09±1.89)μg/m l及(11.80±2.85)μg/m l;AUC分别为(50.98±13.65)μg.h/m l、(93.85±17.82)μg.h/m l及(163.60±31.69)μg.h/m l;t1/2α分别为(1.13±0.62)h、(0.75±0.44)h及(0.71±0.41)h;t1/2β分别为(17.84±5.97)h、(14.05±2.60)h及(14.16±1.72)h;CL s分别为(2.11±0.63)L/h、(2.20±0.40)L/h及(1.90±0.34)L/h;Vc分别为(25.44±6.17)L、(19.48±9.40)L及(18.03±7.24)L。结论注射用盐酸米诺环素在人体内的药动学符合二室模型特征。

Objective To study the pharmacokinetics of minocycline hydrochloride for injection in healthy human. Methods Twelve healthy volunteers were selected to receive a single dose of minocycline 100, 200 and 300mg within 2h infusion in an open randomized threefold cross-over study. There was a week washout in every project. Blood samples were taken for detecting serum concentration before administration and at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24,48, 72h after completion of the intravenous infusion. The concentrations of minocycline in serum were determined by a high-pressure liquid chromatography （HPLC） method. Results Pharmacokinetic profiles were conformed to an open two compartment model analyzed by using 3P97 and the result of HPLC method were as follows： the Cmax of 100, 200, 300mg minocycline at the end of infusion were （3. 11±0. 67）μg/ml, （7.09±1.89）μg/ml and （11.80±2.85）μg/ml; the AUCs were （50.98±13. 65）μg · h/ml, （93.85±17.82）μg· h/ml and （163.60±31.69）μg· h/ml; the t1/2. were （1.13±0.62） h, （0.75±0.44）h and （0.71±0.41）h; the t1/2β were （17.84±5.97）h, （14.05±2.60）h and （114.16±1. 72）h; the CLs were （2.11±-0.63）L/h, （2. 20 ± 0. 40） L/h and （1.90±0.34）L/h; the Vc were （125.44±6. 17）L, （19.48±9.40）L and （18.03±7. 24）L, respectively.