健康人体静脉滴注尼扎替丁的药动学研究

 目的 研究尼扎替丁注射液的药动学。方法 选择20名中国健康成年志愿者，男女各半，单次静滴尼扎替丁注射液100和200 mg及100 mg多次给药。血及尿中药物浓度分别用LC-MS/MS和高效液相色谱测定。利用血药浓度，以DAS软件计算药动学参数；利用尿药浓度计算尿药累积排泄率。结果 受试者静滴尼扎替丁注射液100，200 mg及100 mg多次给药后，主要药动学参数分别是ρmax（1 623.58±429.34），（3 722.78±571.70）和（2 155.47±652.39）μg·L-1，AUC0-8 （2 183.81±545.60），（4 776.04±828.05）和（2 741.56±827.81） μg·h·L-1，AUC0-∞ （2 222.35±553.84）,（4 854.36±837.43）和（2 793.17±828.18）μg·h·L-1，t1/2（1.50±0.23），（1.48±0.16）和（1.62±0.29） h。100 mg单次和100 mg多次给药组经t检验，差异无统计学意义；100和200 mg组除ρmax和AUC与剂量成正比外，其余主要药动学参数组间差异无显著性。静滴尼扎替丁注射液100，200 及100 mg多次给药后,0~12 h内尿药累积排泄率分别为（50.63±8.55）%，（58.30±16.22）%和（54.85±14.58）%，经t检验差异无统计学意义。结论 本品每8 h给药1次，每次静滴100 mg，共给3次，连续给药3 d，可达稳态浓度，多次给药后其药动学行为无异常改变。该制剂平均有50%以上的原型药物从肾脏排出，表明该药主要以原型从肾脏排泄。

Pharmacokinetic Study of Nizatidine in Healthy Volunteers by Intravenous Injection

OBJECTIVE To investigate the pharmacokinetics of nizatidine injections in Chinese healthy volunteers. METHODS Twenty healthy volunteers (10 men and 10 women) were administrated a single dose(100 or 200 mg) and multi-doses (100 mg every time, three times a day for 4 d) of nizatidine injections. The plasma and urine concentrations were determined by LC-MS/MS and HPLC method respectively. The pharmacokinetic parameters were calculated by DAS software and the accumulate urinary excretion rates were acquired by urine concentrations. RESULTS The main pharmacokinetic parameters of the three groups including 100, 200 mg and multi-dose were: ρmax （1 623.58±429.34）,（3 722.78±571.70） and（2 155.47±652.39）μg·L-1, AUC0-8 （2 183.81±545.60）, （4 776.04±828.05） and （2 741.56±827.81） μg·h·L-1， AUC0-∞ （2 222.35±553.84）, （4 854.36±837.43）and （2 793.17±828.18） μg·h·L-1，t1/2 （1.50±0.23）, （1.48±0.16） and （1.62±0.29） h. There were no significant differences in AUC0-t /dose and ρmax /dose between the single-dose groups (100 and 200 mg). There were no remarkable difference in other pharmacokinetics parameters between single-dose and multi-dose group. The accumulate urinary excretion rates (0-12 h) of three groups (100, 200 mg and multi-dose) were（50.63±8.55）%, （58.30±16.22）% and（54.85±14.58）%, respectively, and there were no statistic difference among them. CONCLUSION No accumulation in human body was observed after intravenous drip infusing 100 mg nizatidine injections three times a day for 4 d. Over 50% of the free drugs were eliminated through the kidney.