摘要
目的建立液相色谱-串联质谱法(LC-MS/MS)测定健康人体血浆中的氯诺昔康浓度,研究3种氯诺昔康制剂在健康人体的药动学。方法24名男性健康受试者,按随机三交叉试验设计,清洗期均为7 d,分别口服8 mg氧诺昔康速释片或普通片、或臀部肌内注射8 mg氯诺昔康注射剂,LC-MS/MS电喷雾正离子选择性反应检测血药浓度经时过程;DAS 2.0程序计算氯诺昔康的主要药动学参数。结果氯诺昔康速释片或普通片,及注射剂的主要药动学参数:c_(max)分别为(1 174±246)、(596±158)和(950±230)μg·L^(-1);AUC_(0～24)分别为(4 052±706)、(3 450±966)和(3 838±822)μg·h·L^(-1);AUC_(0～∞)分别为(4 101±715)、(3 543±1 062)和(3 903±854)μg·h·L^(-1);t_(max)分别为(0.5±0.3)、(1.9±1.0)和(0.5±0.3)h;t_(1/2)分别为(3.8±0.7)、(4.1±1.0)和(4.0±0.8)h;MRT分别为(4.6±0.6)、(6.1±1.5)和(5.1±0.8)h;CL(F)分别为(2.0±0.4)、(2.5±0.7)和(2.2±0.5)L·h^(-1);V(F)分别为(11±3)、(14±5)和(11.3±2.1)L。速释片和肌内注射剂的吸收速度和程度无显著差异(P>0.05),并且明显高于普通片剂(P<0.01).结论氯诺昔康血浆样品LC-MS/MS测定法专属、准确、灵敏;测得速释片与肌内注射剂生物等效,与肌内注射剂相比,速释片可改善病人的依从性。
AIM To establish a selective and sensitive LC-MS/MS for the concentration determination of plasma lornoxicam and study the pharmacokinetics of lornoxicam in three formulations of healthy volunteers. METHODS 24 healthy male Chinese volunteers with 3-way crossover design of a 7-day washout period were randomized to receive a single 8 mg dose of lornoxicam rapid release tablets or conventional regular release tablets orally, or 8 mg lornoxicam injection with intramuscular injection at the buttock. The plasma concentrations of lornoxicam were determined through validated LC-MS/MS method. DAS 2.0 program was carried out for the pharmacokinetic analysis. RESULTS The main pharmacokinetics parameters of lornoxicam in human plasma after 8 mg oral rapid release, regular release tablets, and injection were as follow： cmax （1 174 ± s 246）, （596 ± 158） and （950 ± 230） mg·L^-1; AUC0-24 （4 052 ± 706）, （3 450 ± 966） and （3 838 ±822） μg·h·L^-1; AUC0-60 （4 101 ± 715）, （3 543 ±1 062） and （3 903 ±854） μg·h·L^-1; tmax （0.5 ± 0.3）, （1.9 ± 1.0） and （0.5 -± 0.3） h; t1/2 （3.8±0.7）, （4.1 ± 1.0） and （4.0±_0.8） h; MRT （4.6±0.6）, （6.1 _± 1.5） and （5.1 ± 0.8） h; CL （F） （2.0±0.4）, （2.5 ±0.7） and （2.2_±0.5） L·h^-1; V （F） （11 ±3）, （14±5） and （11.3 ± 2.1 ） L, respectively. No significant difference was found between the pharmacokinetics of the rapid release tablets and the injection with the absorption rates and bioavailabilities of the both much better than the conventional regular release tablets. CONCLUSION The established LC-MS/MS test method for lornoxicam sample of human plasma is specific, sensitive, and accurate and the lornoxicam rapid release tablets is bioequivalent with the lornoxicam injection with further improvement of patient compliance.
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2008年第1期20-23,共4页
Chinese Journal of New Drugs and Clinical Remedies
