中药0期临床药代动力学试验探索
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摘要
目的:以舒血宁注射液为示范,探索中药进行0期临床药代动力学试验的可行性。方法:检测健康受试者在静脉滴注微剂量舒血宁注射液后的血药浓度;按照倍数分布关系,以单次给药爬坡的方式摸索血药浓度的最小检测剂量,计算药动学参数;以临床用药剂量为对照,考察药动学规律。结果:在舒血宁注射液微剂量组的药动学检测中,血药浓度低于检测下限;单次给药爬坡组在相当于临床给药剂量的1/25以上时,可以检测到血药浓度。结论:与临床给药剂量组相比,低剂量给药具有大致相同的药物代谢趋势,0期临床药代动力学试验。
This paper was aimed to explore the possibility for pharmacokinetics experiment of phase 0 clinical trial in traditional Chinese medicine(TCM). The plasma concentration of volunteers after being injected with micro-dose Shuxuening Injection was tested. According to multiple distributions, the minimum detectable dose was explored by increasing single dose, in order to calculate the pharmacokinetics parameters and to find out the law in the pharmacokinetics experiment by comparing with the clinical dosage. The results showed that in the micro-dose group,concentrations cannot be detected. In the single-dose climbing group, the concentration was tested out above 1/25 of clinical dosage. It was concluded that compared with the clinical group, low-dose has similar metabolic tendency of drugs. It is possible to conduct pharmacokinetics experiment of phase 0 clinical trial in TCM.
This paper was aimed to explore the possibility for pharmacokinetics experiment of phase 0 clinical trial in traditional Chinese medicine(TCM). The plasma concentration of volunteers after being injected with micro-dose Shuxuening Injection was tested. According to multiple distributions, the minimum detectable dose was explored by increasing single dose, in order to calculate the pharmacokinetics parameters and to find out the law in the pharmacokinetics experiment by comparing with the clinical dosage. The results showed that in the micro-dose group,concentrations cannot be detected. In the single-dose climbing group, the concentration was tested out above 1/25 of clinical dosage. It was concluded that compared with the clinical group, low-dose has similar metabolic tendency of drugs. It is possible to conduct pharmacokinetics experiment of phase 0 clinical trial in TCM.
引文
1 Kinders R,Parchment R E,Ji J,et al.Phase 0 clinicaltrials in cancer drug development:from FDA guidance toclinical practic.MolInterv,2007,7(6):325-334.
2 Cho D Y,Bae,Soo H,Shon J H,et al.High-sensitive LC-MS/MS method for the simultaneous determination of mirodenafil and its major metabolite,SK-3541,in human plasma:Application to microdose clinical trials of mirodenafil.J Sep Sci,2013,36(5):840-848.
3 Pasqualetti G,Gori G C,et al.Healthy volunteers and early phases of clinical experimentation.Eur J Clin Pharmacol,2010,66(7):647-653.
4 Faunce T A,Faunce T A.Global clinical trials:effective implementation and management.JAMA,2012,307(307):2105.
5 Marchetti S,Schellens J H.The impact of FDA and EMEA guidelines on drug development in relation to Phase 0 trials.Br J Cancer,2007,97(5):577-581.
6 Donawho C K,Luo Y,Luo Y,et al.ABT-888,an orally active poly(ADP-ribose)polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models.Clin Cancer Res,2007,13(9):2728-37.
7 Arrowsmith J,Miller P.Trial Watch:Phase II and Phase III attrition rates 2011-2012.Nat Rev Drug discov,2013,12(8):569.
8 Yang B,Meng Z Y,Yan L P,et al.Pharmacokinetics and metabolism of1,5-dicaffeoylquinic acid in rats following a single intravenous administration.J Pharm Biomed Anal,2006,40(2):417-422.
9谢雁鸣,魏戌,张占军,等.0期临床试验与中药注射剂上市后临床安全性再评价.中国中药杂志,2011,36(20):2874-2876.
10任艳萍.中药矮地茶质量控制与体内代谢及舒血宁注射液的多组分测定与药动学研究.石家庄:河北医科大学.2013.
2 Cho D Y,Bae,Soo H,Shon J H,et al.High-sensitive LC-MS/MS method for the simultaneous determination of mirodenafil and its major metabolite,SK-3541,in human plasma:Application to microdose clinical trials of mirodenafil.J Sep Sci,2013,36(5):840-848.
3 Pasqualetti G,Gori G C,et al.Healthy volunteers and early phases of clinical experimentation.Eur J Clin Pharmacol,2010,66(7):647-653.
4 Faunce T A,Faunce T A.Global clinical trials:effective implementation and management.JAMA,2012,307(307):2105.
5 Marchetti S,Schellens J H.The impact of FDA and EMEA guidelines on drug development in relation to Phase 0 trials.Br J Cancer,2007,97(5):577-581.
6 Donawho C K,Luo Y,Luo Y,et al.ABT-888,an orally active poly(ADP-ribose)polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models.Clin Cancer Res,2007,13(9):2728-37.
7 Arrowsmith J,Miller P.Trial Watch:Phase II and Phase III attrition rates 2011-2012.Nat Rev Drug discov,2013,12(8):569.
8 Yang B,Meng Z Y,Yan L P,et al.Pharmacokinetics and metabolism of1,5-dicaffeoylquinic acid in rats following a single intravenous administration.J Pharm Biomed Anal,2006,40(2):417-422.
9谢雁鸣,魏戌,张占军,等.0期临床试验与中药注射剂上市后临床安全性再评价.中国中药杂志,2011,36(20):2874-2876.
10任艳萍.中药矮地茶质量控制与体内代谢及舒血宁注射液的多组分测定与药动学研究.石家庄:河北医科大学.2013.