摘要
目的 研究三氮脒、三氮脒脂质体和复方三氮脒注射液 (TRYPAN)在兔体内的药代动力学和组织残留量。 方法 应用三氮脒、三氮脒脂质体和 TRYPAN给兔单剂量 (3.5 mg/ kg体重 )肌肉注射 ,用反相高效液相色谱法测定给药不同时间后兔体内的血浆药物浓度和组织中的药物残留量 ,并利用 3p87药代动力学软件进行分析。 结果 三氮脒、三氮脒脂质体和 TRYPAN在兔体内的药代动力学均符合一级吸收二室模型 ,其主要药代动力学参数依次分别为 :达峰时间 (Tmax) (0 .4 5± 0 .12 ) h、(3.36± 0 .75 ) h、(2 .4 2± 0 .6 8) h,最高血药浓度 (Cmax) (3.85± 0 .4 1)、(3.0 1± 0 .16 )、(3.4 3± 0 .2 7) μg/ ml,消除相半衰期 (t1 / 2β) (87.0 3± 18.72 ) h、(136 .14± 2 0 .14 ) h、(10 4 .4 0± 32 .18) h,药时曲线下面积(AUC) (2 2 4 .72± 92 .15 )、(44 0 .90± 87.73)、(2 94 .35± 73.92 ) μg/ ml.h。三氮脒脂质体与三氮脒和 TRYPAN相比 ,达峰时间 (Tmax)分别延长了 2 .91h、0 .94 h,峰浓度 (Cmax)分别降低了 0 .84、0 .4 2 μg/ ml,消除相半衰期 (t1 / 2β)分别延长了 4 9.11h、31.74 h,药时曲线下面积 (AUC)分别增大了 2 16 .18、14 6 .5 5μg/ ml.h,因此具有吸收缓慢、毒副作用小、消除缓慢和作用时间?
Objective To study the pharmacokinetics and tissue residues of diminazene, diminazene liposomes and diminazene compound(TRYPAN) in rabbits. Methods The concentrations in plasma and tissue residues of diminazene, diminazene liposomes and TRYPAN in rabbits were determined following single intramuscular administration of 3.5 mg/kg body weight by using reversed phase high performance liquid chromatography, and analyzed by 3p87 pharmacokinetic software. Results The pharmacokinetics of diminazene, diminazene liposomes and TRYPAN in rabbits were fitted to a two compartment model with first order absorption. Their main pharmacokinetic parameters were as follows: T max (0.45±0.12) h, (3.36±0.75) h, (2.42±0.68) h,C max (3.85±0.41), (3.01±0.16), (3.43±0.27) μg/ml, t 1/2β (87.03±18.72)h, (136.14±20.14) h, (104.40±32.18) h, AUC (224.72± 92.15 ), (440.90±87.73), (294.35±73.92) μg/ml·h respectively. The T max of diminazene liposomes was 2.91 h, 0.94 h longer than those of the diminazene and TRYPAN respectively. The C max of diminazene liposomes was 0.84, 0.42 μg/ml lower than those of the diminazene and TRYPAN respectively. The t 1/2β of diminazene liposomes was 49.11 h, 31.74 h longer than those of the diminazene and TRYPAN respectively. The AUC of diminazene liposomes was 216.18, 146.55 μg/ml·h bigger than those of the diminazene and TRYPAN respectively. So the diminazene liposomes had the features of slow absorption, small toxic and side effects, slow elimination and long effecting time. The results of the tissue residues of diminazene, diminazene liposomes and TRYPAN in rabbits showed that the highest residues were in liver and the lowest residues were in brain. The tissue residues of diminazene liposomes in liver, spleen and brain were higher than those of the other two groups,this related with the features of the liposomes. Furthermore, the anti parasite activity of drug in liver, spleen and brain were strengthened. Conclusion Diminazene liposomes were more effective than diminazene and TRYPAN in effecting time, toxic and side effects and anti parasite activity in liver, spleen and brain.
出处
《中国寄生虫病防治杂志》
CSCD
2002年第6期367-369,共3页
Chinese Journal of Parasitic Disease Control
