家犬单剂量和多剂量口服阿昔莫司缓释制剂的药代动力学和生物等效性研究

The pharmacokinetics and bioequivalence of acipimox sustained-release tablets after a single and multiple oral administration in healthy dogs

目的 研究阿昔莫司缓释片在家犬体内单剂量和多剂量的药代动力学和生物等效性。方法 测定6只家犬单剂量和多剂量口服缓释片和普通胶囊后的血药浓度。结果 阿昔莫司的药时曲线符合非隔室模型。单剂量给药后,缓释片和普通胶囊的AUC分别为(158±30)和( 147±37 )μg·h·mL-1;Tmax分别为( 4. 3±0 .8 )和( 2 .6±1. 3)h;Cmax分别为(29±6)和(42±10)μg·mL-1;T1 /2分别为( 2 3±0 7 )和( 1.60±0 .10 )h;MRT分别为( 6. 0±0 .8)和(3 .9±0 .7)h;Fr为(108±16)%。多剂量给药后,缓释片和普通胶囊的AUC分别为(209±23)和(195±26)μg·h·mL-1;Tmax分别为(6. 3±0 .8)和(3. 4±1 .5)h;Cmax分别为(27±4)和(36±5)μg·mL-1;Cmin分别为(2 .2±1 .0)和(0 .20±0 .20)μg·mL-1;Cav分别为(8. 7±1. 0)和(8 .1±1 .1)μg·mL-1;FI分别为(293±73)%和(448±91)%;Fr为(114±19)%。结论 单剂量实验的双单侧检验结果表明:缓释片和普通胶囊生物等效;缓释片具有良好的缓释效果。多剂量实验结果表明:缓释片和普通胶囊生物等效;缓释片的波动系数优于普通胶囊。

Aim To study the pharmacokinetics and bioequivalence of acipimox sustained-release tablets (SRT) after a single and multiple oral dose in healthy dogs. Methods The plasma concentrations of of SRT and reference capsules with a single and multiple oral doses. Results The drug concentration-time profiles fitted to a noncompartment model. After a single dose administration of sustained-release tablets and capsules,the pharmacokinetic parameters were as follows: AUC were (158±30) and (147±37) μg·h·mL^(-1); T (max) were (4.3±0.8) and (2.6±1.3) h; C (max) were (29±6) and (42±10) μg·mL^(-1); T (1/2) were (2.3±0.7) and (1.60±0.10) h; MRT were (6.0±0.8) and (3.9±0.7) h, respectively. The relative bioavailability of the sustained-release tablet was (108±16)%. After a multiple oral administration of sustained-release tablets and capsules,the pharmacokinetic parameters were as follows: AUC were (209±23) and (195±26) μg·h·mL^(-1); T (max) were (6.3±0.8) and (3.4±1.5) h; C (max) were (27±4) and (36±5) μg·mL^(-1); C (min) were (2.2±1.0) and ((0.20±)0.20) μg·mL^(-1); C (av) were (8.7±1.0) and (8.1±1.1) μg·mL^(-1); FI were (293±73)% and (448±91)%, respectively. The relative bioavailability of the sustained-release tablet was (114±19)%. Conclusion The results of two one-side test from single dose administration shown that two preparations were bioequivalent. The C (max) of sustained-release tablet was lower than that of capsules, while the T (max) and MRT of sustained-release tablet were higher than that of capsule, which indicating a good retarding effect. The results from multiple dose administration also shown that two preparations were bioequivalent and the DF of sustained-release tablet was significant lower than that of capsule.