中国临床药理学杂志2024，Vol.40Issue(11)：1633-1637,5.DOI:10.13699/j.cnki.1001-6821.2024.11.019
Naldemedine在中国健康成年人的安全性、耐受性和药代动力学特征研究
Safety,tolerability and pharmacokinetic characterization of naldemedine in Chinese healthy volunteers
摘要
Abstract
Objective To evaluate the safety,tolerability and pharmacokinetic profiles of naldemedine in Chinese healthy adult subjects after single and multiple administrations.Methods After single and multiple oral administrations of naldemedine to 10 healthy Chinese subjects,the plasma concentrations of naldemedine and its metabolite(nor-naldemedine)were measured by liquid chromatography-mass spectrometry,and the pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.3.1 software.Results Compared with single administration,naldemedine showed no significant change in the tmax(1.06 h for single and 1.08 h for multiple)and Cmax(4.16 ng·mL-1 for single and 4.11 ng·mL-1 for multiple),higher AUC0-τ than that of single(23.88 ng·h·mL-1 for single and 28.93 ng·h·mL-1 for multiple),slightly prolonged t1/2(9.26 h for single,12.50 h for multiple),there was a slight drug accumulation after multiple doses(accumulation ratio of 0.99 for Cmax and 1.22 for AUC);t1/2(18.10 h for single,29.30 h for multiple),Cmax(0.19 ng·mL-1 for single,0.38 ng·mL-1 for multiple),and AUC0-τ(3.13 ng·h·mL-1 for single,6.02 ng·h·mL-1 for multiple)were all significantly elevated with nor-naldemedine,and the tmax(single was 3.49 h and multiple was 3.56 h)did not change significantly.The Cmax ratio and AUC ratio of metabolites to naldemedine were significantly elevated,and accumulation was present after multiple administrations(accumulation ratio of 2.01 for Cmax and 1.95 for AUC).All adverse events that occurred after treatment were mild.Conclusion After multiple oral administrations of 0.2 mg naldemedine tablets to Chinese healthy subjects(single dose on day 1 and once daily on days 4-13),the drug was eliminated rapidly with mild accumulation,and reached a steady state before the second dose of the multiple-dosing phase,and the product has a favorable safety and tolerability profiles.关键词
naldemedine/nor-naldemedine/中国健康受试者/药代动力学/安全性Key words
naldemedine/nor-naldemedine/Chinese healthy adult subjects/pharmacokinetics/safety分类
医药卫生引用本文复制引用
杨雅茹,郑亮,张炜,豆红红,藤谷航平,窪田竜二,胡伟..Naldemedine在中国健康成年人的安全性、耐受性和药代动力学特征研究[J].中国临床药理学杂志,2024,40(11):1633-1637,5.基金项目
安徽省临床医学研究转化专项基金资助项目(202304295107020021) （202304295107020021）
安徽省转化医学研究院科研基金资助项目(2022zhyx-B10) （2022zhyx-B10）
