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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。
Pharmacokinetics of 6β-naltrexol administered in single and continuous intramuscular injections in dogs. Beagle dogs (n = 4) intramuscular injection of 6β-naltrexone 0.2 mg.kg-1, once daily for 7 days. Plasma 6β-naltrexol concentrations were determined by reversed-phase high performance liquid chromatography-electrochemical detection. Beagle dogs single (first) and continuous administration (last) after the change of plasma concentration over time are in line with the first-class absorption of two-compartment model of extravascular administration (R2> 0.999), pharmacokinetic parameters (81.65 ± 5.61) and (79.82 ± 10.5) ng.mL-1 for t1 / 2α (0.26 ± 0.23) and (0.19 ± 0.18) h, t1 / 2β for 4.77 ± 1.65 and 5.79 ± 1.50 for h (0.27 ± 0.07) and (0.18 ± 0.08) h, CLs (1.20 ± 0.06) and (1.12 ± 0.07) L.kg -1 h -1, V / Fc 1.94 ± 0.15 and 2.10 ± 0.27 ) L.kg-1, AUC0-t (166.82 ± 7.68) and (173.23 ± 9.49) ng.h.mL-1. There was no significant difference in pharmacokinetic parameters between the first and last dose (P> 0.05). During continuous dosing, the average peak plasma concentration and trough concentration were (79.03 ± 10.3) and (1.50 ± 0.93) ng.mL-1, respectively. The results showed that the pharmacokinetics of 6β-naltrexol in dogs was in accordance with the first-order absorption two-compartment model and the corresponding pharmacokinetic parameters were obtained. Continuous administration had no effect on the metabolism of prototype drugs.