{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T23:56:37Z","timestamp":1785455797839,"version":"3.56.0"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,10,17]],"date-time":"2018-10-17T00:00:00Z","timestamp":1539734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Shanghai Pudong New District Technology Development Postdoctoral Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>To evaluate the potential ethnic differences in the pharmacokinetics (PK) and pharmacodynamics (PD) of evolocumab in Caucasian and Asian populations using population PK\/PD modelling analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data from different ethnic groups in 5 Phase I clinical trials, including two American studies, one Japanese study and two Chinese studies, were chosen for model building and evaluation. A target\u2010mediated drug disposition model together with an indirect response model best captured evolocumab binding and the removal of unbound proprotein convertase subtilisin\/kexin type 9 (PCSK9) as well as a reduction in circulating low\u2010density lipoprotein cholesterol (LDL\u2010C). Ethnicity and other related factors (body weight, target expression level etc.) were analysed as potential covariates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The estimated linear clearance and volume of evolocumab were 0.24\u00a0l\u00a0day<jats:sup>\u20131<\/jats:sup> and 2.75\u00a0l, respectively, which was consistent with the previous modelling results from the American trials. The time course of the LDL\u2010C reduction was described by an indirect response model with the elimination rate of LDL\u2010C being modulated by unbound PCSK9. The concentration of unbound PCSK9 associated with the half\u2010maximal inhibition of LDL\u2010C elimination was 1.28\u00a0nmol\u00a0l<jats:sup>\u20131<\/jats:sup>. Both the PK and PD characteristics were consistent between the Caucasian and Asian populations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The target\u2010mediated drug disposition model successfully described the PK and PD characteristics of evolocumab, and this analysis found no significant differences in the PK\/PD relationship for its LDL\u2010C lowering effects between Caucasians and Asians.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13767","type":"journal-article","created":{"date-parts":[[2018,9,18]],"date-time":"2018-09-18T06:48:15Z","timestamp":1537253295000},"page":"114-125","source":"Crossref","is-referenced-by-count":17,"title":["Lack of ethnic differences in the pharmacokinetics and pharmacodynamics of evolocumab between Caucasian and Asian 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Lu","sequence":"additional","affiliation":[{"name":"Amgen Asia R&amp;D Center  Zhangjiang High\u2010Tech Park Shanghai 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