血小板生成素受体激动剂avatrombopag的药理作用及临床评价
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摘要
avatrombopag是第2代口服生物可利用小分子血小板生成素受体激动剂,可以模拟血小板生成素的作用,增加血小板的产生。2018年5月FDA批准avatrombopag上市,用于成人慢性肝病患者血小板减少症的治疗。临床试验表明其具有良好的安全性和有效性,主要不良反应有发热、腹痛、恶心、头痛、疲倦和手足水肿等。本文对其药理作用、药动学、临床研究及不良反应等做一综述。
Avatrombopag is the second generation of oral bioavailable small molecule thrombopoietin receptor agonist that mimics the action of thrombopoietin and increases the production of platelet. In May 2018,avatrombopag was approved by the US FDA for the treatment of thrombocytopenia in adults with chronic liver disease. Clinical trials showed that the drug was safe and well tolerated. The main adverse reactions were fever,abdominal pain,nausea,headache,fatigue and edema. In this article,the pharmacological action,pharmacokinetics,clinical research and adverse reactions of avatrombopag were reviewed.
Avatrombopag is the second generation of oral bioavailable small molecule thrombopoietin receptor agonist that mimics the action of thrombopoietin and increases the production of platelet. In May 2018,avatrombopag was approved by the US FDA for the treatment of thrombocytopenia in adults with chronic liver disease. Clinical trials showed that the drug was safe and well tolerated. The main adverse reactions were fever,abdominal pain,nausea,headache,fatigue and edema. In this article,the pharmacological action,pharmacokinetics,clinical research and adverse reactions of avatrombopag were reviewed.
引文
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[2]赵西平.慢性肝病患者血小板减少发生机制及治疗[J].临床血液学杂志,2016,29(1):11-15.
[3]PECK-RADOSAVLJEVIC M.Thrombocytopenia in chronic liver disease[J].Liver Int,2017,37(6):778-793.
[4]KUTER DJ.The biology of thrombopoietin and thrombopoietin receptor agonists[J].Int J Hematol,2013,98(1):10-23.
[5]朱翊,李江涛,傅得兴.促血小板生成剂的研究进展[J].中国新药杂志,2013,22(7):782-786.
[6]FDA.Avatrombopag[EB/OL].[2018-10-10].https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210238s000lbl.pdf.
[7]TERRAULT NA,HASSANEIN T,HOWELL CD,et al.Phase II study of avatrombopag in thrombocytopenic patients with cirrhosis undergoing an elective procedure[J].J Hepatol,2014,61(6):1253-1259.
[8]TERRAULT N,CHEN YC,IZUMI N,et al.Avatrombopag before procedures reduces need for platelet transfusion in patients with chronic liver disease and thrombocytopenia[J].Gastroenterology,2018,155(3):705-718.
[9]NOMOTO M,PASTINO G,REGE B,et al.Pharmacokinetics,pharmacodynamics,pharmacogenomics,safety,and tolerability of avatrombopag in healthy Japanese and white subjects[J].Clin Pharmacol Drug Dev,2018,7(2):188-195.
[10]FDA.Avatrombopag[EB/OL].[2018-10-22].https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2018/210238Orig1s000ltr.pdf.
[11]AFDHAL NH,GIANNINI EG,TAYYAB G,et al.Eltrombopag before procedures in patients with cirrhosis and thrombocytopenia[J].N Engl J Med,2012,367(8):716-724.
[12]FDA.Eltrombopag[EB/OL].[2018-10-10].https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022291s020,207027s005lbl.pdf.
[13]NOMOTO M,ZAMORA CA,SCHUCK E,et al.Pharmacokinetic/pharmacodynamic drug-drug interactions of avatrombopag when coadministered with dual or selective CYP2C9 and CYP3Ainteracting drugs[J].Br J Clin Pharmacol,2018,84(5):952-960.
[14]张珂,雷慧,陈曦,等.血小板生成素受体激动剂治疗免疫性血小板减少症的新药研发进展[J].中国新药杂志,2017,26(20):2380-2385.
[2]赵西平.慢性肝病患者血小板减少发生机制及治疗[J].临床血液学杂志,2016,29(1):11-15.
[3]PECK-RADOSAVLJEVIC M.Thrombocytopenia in chronic liver disease[J].Liver Int,2017,37(6):778-793.
[4]KUTER DJ.The biology of thrombopoietin and thrombopoietin receptor agonists[J].Int J Hematol,2013,98(1):10-23.
[5]朱翊,李江涛,傅得兴.促血小板生成剂的研究进展[J].中国新药杂志,2013,22(7):782-786.
[6]FDA.Avatrombopag[EB/OL].[2018-10-10].https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210238s000lbl.pdf.
[7]TERRAULT NA,HASSANEIN T,HOWELL CD,et al.Phase II study of avatrombopag in thrombocytopenic patients with cirrhosis undergoing an elective procedure[J].J Hepatol,2014,61(6):1253-1259.
[8]TERRAULT N,CHEN YC,IZUMI N,et al.Avatrombopag before procedures reduces need for platelet transfusion in patients with chronic liver disease and thrombocytopenia[J].Gastroenterology,2018,155(3):705-718.
[9]NOMOTO M,PASTINO G,REGE B,et al.Pharmacokinetics,pharmacodynamics,pharmacogenomics,safety,and tolerability of avatrombopag in healthy Japanese and white subjects[J].Clin Pharmacol Drug Dev,2018,7(2):188-195.
[10]FDA.Avatrombopag[EB/OL].[2018-10-22].https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2018/210238Orig1s000ltr.pdf.
[11]AFDHAL NH,GIANNINI EG,TAYYAB G,et al.Eltrombopag before procedures in patients with cirrhosis and thrombocytopenia[J].N Engl J Med,2012,367(8):716-724.
[12]FDA.Eltrombopag[EB/OL].[2018-10-10].https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022291s020,207027s005lbl.pdf.
[13]NOMOTO M,ZAMORA CA,SCHUCK E,et al.Pharmacokinetic/pharmacodynamic drug-drug interactions of avatrombopag when coadministered with dual or selective CYP2C9 and CYP3Ainteracting drugs[J].Br J Clin Pharmacol,2018,84(5):952-960.
[14]张珂,雷慧,陈曦,等.血小板生成素受体激动剂治疗免疫性血小板减少症的新药研发进展[J].中国新药杂志,2017,26(20):2380-2385.