摘要
研究6β-纳曲醇单次和连续肌内注射给药在犬体内的药代动力学。Beagle犬(n=4)肌内注射6β-纳曲醇0.2 mg.kg-1,每日1次,连续7日。用反相高效液相-电化学检测法测定血浆6β-纳曲醇浓度。Beagle犬单次(第一次)及连续给药(最后一次)后的血药浓度经时变化过程均符合血管外给药一级吸收二室模型(R2>0.999),药代动力学参数分别为t1/2α(0.26±0.23)和(0.19±0.18)h,t1/2β(4.77±1.65)和(5.79±1.50)h,Cmax(81.65±5.61)和(79.82±10.5)ng.mL-1,tpeak(0.27±0.07)和(0.18±0.08)h,CLs(1.20±0.06)和(1.12±0.07)L.kg-1.h-1,V/Fc(1.94±0.15)和(2.10±0.27)L.kg-1,AUC0-t(166.82±7.68)和(173.23±9.49)ng.h.mL-1。第一次和最后一次给药的药代动力学参数无显著性差异(P>0.05)。连续给药期间,血药峰浓度和谷浓度的平均值分别为(79.03±10.3)和(1.50±0.93)ng.mL-1。结果显示,6β-纳曲醇在犬体内的药物代谢过程符合一级吸收二室模型,得到了相应的药代动力学参数;连续给药对原形药物代谢过程基本无影响。
The pharmacokinetics of 6β-naltrexol （6β-NOL） following single intramuscular administration and multiple intramuscular injection once per day for seven days was studied in 4 Beagle dogs. Plasma concentration of 6β-NOL in dogs was analyzed by a combination of high performance liquid chromatography （HPLC） and electrochemical detection with naloxone （NLX） as internal standard. After single intramuscular injection of 0.2 mg.kg^-1 6β-NOL, the plasma concentration-time curve of the drug was found to fit to a two compartment model with first-order absorption. The main parameters of single dosing were as follows： t1/2α was （0.26 ± 0.23） h, t1/2β was （4.77± 1.65） h, Cmax was （81.65 ± 5.61） ng.mL^-1, tpeak was （0.27 ± 0.07） h, CLs was （1.20±0.06） L.kg^-1.h^-1, V/Fc was （1.94 ± 0.15） L.kg^-1, and AUC0-t was （166.82 ± 7.68） ng.h.mL^-1, separately. After multiple intramuscular injection of 0.2 mg.kg^-1 6β-NOL once per day for seven days, the plasma concentration-time curve of the drug fitted to a two compartment model with first-order absorption too. The main parameters of the last dosing were as follows： tu2a was （0.19 ± 0.18） h, t~/zB was （5.79 ± 1.50） h, Cma~ was （79.82± 10.5） ng.mL^-1, tpeak was （0.18 ± 0.08） h, CLs was （1.12 ± 0.07） L.kg^-1h^-1, V/Fe was （2.10 ± 0.27） L.kg^-1, and AUC0-t was （173.23± 9.49） ng.h.mL^-1, separately. The difference of the parameters between the first and the last dosing was not significant, showing that the plasma kinetics of 6β-naltrexol was not changed after multiple administrations. In the course of multiple administration, the peak and valley concentration of plasma 6β-naltrexol were （79.03 ± 10.3） and （1.50 ± 0.93） ng.mL^-1, respectively. No clear adverse events were noted during this study. These results showed that plasma 6β-naltrexol fits to a two compartment model with first-order absorption in dog after intramuscular administration and their pharmacokinetic parameters were repo
出处
《药学学报》
CAS
CSCD
北大核心
2009年第7期722-725,共4页
Acta Pharmaceutica Sinica
基金
北京市科技计划资助项目(H020220060190)
