含毒性药材马钱子的妇健阴道泡腾片BeagIe犬阴道给药毒代动力学

来源 :中国药理学与毒理学杂志 | 被引量 : 0次 | 上传用户:wenlingqiang6268047
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目的 研究含毒性药材马钱子的妇健阴道泡腾片阴道给药,在Beagle犬体内的代谢动力学特征及其在体内的蓄积.方法 妇健阴道泡腾片25.47,84.90和169.80 mg·kg-1 Beagle犬阴道给药1个月,分别于首次给药和末次给药0.25,0.5,1,2,4,6,8,10,12和24 h采血,并用API 5500型串联质谱仪检测血浆中士的宁浓度.结果 妇健阴道泡腾片25.47,84.90和169.80 mg·kg-1组Beagle犬首次给药后,平均AUC0-t值分别为2.44±0.98,7.30±0.50和(5.54±2.71)μg·L-1·h;平均Cmax值分别为0.58±0.22,1.79±0.41和(1.22±0.80)μg·L-1;平均t1/2值分别为2.53±0.38,2.26±0.54和(2.69±1.07)h.末次给药后,妇健阴道泡腾片3个剂量组Beagle犬平均AUC0-t值分别为3.10±0.60,6.91±2.44和(9.15±4.47)μg·L-1·h;平均Cmax值分别为0.80±0.14,1.68±0.60和(1.63±0.77)μg·L-1;平均t1/2值分别为2.26±0.47,2.36±0.30和(4.05±0.75)h.结论 含毒性药材马钱子妇健阴道泡腾片连续给药1个月,随给药时间延长,在Beagle犬体内士的宁的暴露量随剂量增加不呈线性动力学关系,并可能有饱和吸收趋势,给药期内均无药物蓄积.“,”OBJECTIVE To study the pharmacokinetic features of Fujian vaginal effervescent tablets and their accumulation in Beagle dogs. METHODS During the one-month long-term toxicity test of vaginal effervescent tablets, the blood samples of Beagle dogs were drawn at different time on the first day and the last day respectively for the dose groups of 25.47, 84.90 and 169.80 mg· kg-1 before they were tested by API 5500 LC-MS/MS for plasma concentration. RESULTS The main pharmacokinetic parameters of the first administration for 25.47, 84.90 and 169.80 mg · kg-1 groups were as follows:AUC0-t average was 2.44 ± 0.98, 7.30 ± 0.50 and (5.54 ± 2.71)μg · L-1 · h, respectively;Cmax average was 0.58 ± 0.22, 1.79 ± 0.41 and (1.22 ± 0.80) μg · L-1, respectively; t1/2 average was 2.53 ± 0.38, 2.26 ± 0.54 and (2.69 ± 1.07) h, respectively. The main pharmacokinetic parameters of the last administration for the above three groups were as fol ows:AUC0-t average was 3.10±0.60, 6.91±2.44 and (9.15±4.47)μg·L-1·h, respectively;Cmax average was 0.80 ± 0.14, 1.68 ± 0.60 and (1.63 ± 0.77) μg · L-1, respectively; t1/2 average was 2.26 ± 0.47, 2.36±0.30 and (4.05±0.75) h, respectively. CONCLUSION No linear relationship exists between AUC0-t average, Cmax average and administration dosage for each dose group. Therefore, threre is no risk of accu?mulation during long-term administration with strychnine via Fujian vaginal effervescent tablets.
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