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 |
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引用本文: | 颜玲娣,刘 军,董华进,崔孟珣,姚霞君,柳用绍,龚正华,宫泽辉. 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[J]. 药学学报, 2009, 44(7): 722-725 |
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作者姓名: | 颜玲娣 刘 军 董华进 崔孟珣 姚霞君 柳用绍 龚正华 宫泽辉 |
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作者单位: | (1. 军事医学科学院毒物药物研究所, 北京 100850; 2. 解放军第291医院药械科, 内蒙古 包头, 014040) |
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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。
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关 键 词: | 6β-纳曲醇 血浆 药代动力学 单次给药 多次给药 高效液相色谱 |
Pharmacokinetics of 6β-naltrexol after single and multiple intramuscular injections in Beagle dogs |
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Abstract: | 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: t1/2α was (0.19 ± 0.18) h, t1/2β was (5.79 ± 1.50) h, Cmax was (79.82 ± 10.5) ng·mL−1, tpeak was (0.18 ± 0.08) h, CLs was (1.12 ± 0.07) L·kg−1·h−1, V/Fc 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 reported. There was no remarkable change on plasma pharmacokinetics of 6β-naltrexol after multiple intramuscular administrations. |
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Keywords: | 6&beta -naltrexol plasma pharmacokinetics single dose multiple dose HPLC |
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