健康志愿者肌注盐酸美普他酚注射剂后的药动学特征

Pharmacokinetic characteristics after intramuscular meptazinol hydrochloride injection in healthy volunteers

目的研究盐酸美普他酚注射剂在中国健康受试者中单次和多次给药后的药动学特征。方法纳入12名健康受试者按标准三阶段交叉试验方案设计,分别以100、75、50 mg的剂量单次给药;以75 mg剂量多次给药。用LC-MS/MS法测定血浆中美普他酚的浓度,以DAS 2.0软件进行数据处理,求算药动学参数。结果盐酸美普他酚注射剂3个剂量组的AUC_(0→12h)分别为(1 845.54±340.78)、(1 407.32±344.18)和(954.26±208.74)μg·h·L^(-1);AUC_(0→∞)分别为(1 891.41±347.08)、(1 447.85±367.57)和(988.98±226.91)μg·h·L^(-1);ρ_(max)分别为(910.03±240.57)、(700.70±116.04)和(490.86±141.09)μg·L^(-1);t_(max)分别为(0.26±0.09)、(0.30±0.11)和(0.24±0.06)h;t_(1/2)分别为(2.42±0.36)、(2.51±0.42)和(2.61±0.58)h。多次给药无明显蓄积。结论肌注50~100 mg盐酸美普他酚后的AUC_(0→12h)、AUC_(0→∞)、ρ_(max)随剂量增加而增加。

AIM To study the pharmacokinetic characteristics of meptazinol hydrochloride injection, with single or multiple doses in Chinese healthy volunteers. METHODS Twelve Chinese healthy volunteers were enrolled in the study in accordance with the three-period crossover trial protocol. Meptazinol was intramuscularly injected into the sub- jects, with a single dose of 100 mg or 75 mg or 50 mg once respectively and multiple doses of 75 mg. The plasma con-centrations of meptazinol were assessed and data were analyzed automatically with DAS 2.0 pharmacokinetic program. RESULTS The parameters of meptazinol were as follows： AUC0→12h,（1 845.54±340.78）, （1 407.32±344.18） and （954.26 ± 208.74） μg·h·L^-1;AUC0→∞, （1 891.41 ± 347.08）, （1 447.85 ± 367.57） and （988.98 ± 226.91） μg·h·L^-1;ρmax, （910.03 ± 240.57）, （700.70 ± 116.04） and （490.86 ± 141.09）μg·L^-1; tmax, （0.26 ± 0.09）, （0.30±0.11） and （0.24±0.06）h; t1/2, （2.42±0.36）, （2.51±0.42）and （2.61±0.58）h,respectively. CON-CLUSION The pharmacokinetic parmneters such as AUC0~12h, AUC0→∞, ρmax were proportional to dose between 50 to 100 mg in Chinese healthy volunteers.