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Lack of ethnic differences in the pharmacokinetics and pharmacodynamics of evolocumab between Caucasian and Asian populations
| Content Provider | Scilit |
|---|---|
| Author | Wang, Chen Zheng, Qingshan Zhang, Mingqiang Lu, Hong |
| Copyright Year | 2018 |
| Description | Journal: British journal of clinical pharmacology Aim 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. Methods 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‐mediated drug disposition (TMDD) 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‐density lipoprotein cholesterol (LDL‐C). Ethnicity and other related factors (body weight, target expression level, etc.) were analysed as potential covariates. Results The estimated linear clearance and volume of evolocumab were 0.24 L/day and 2.75 L, respectively, which was consistent with the previous modelling results from the American trials. Detailed parameters are shown in Table 2. The time course of the LDL‐C reduction was described by an indirect response model with the elimination rate of LDL‐C being modulated by unbound PCSK9. The concentration of unbound PCSK9 associated with the half‐maximal inhibition (IC50) of LDL‐C elimination was 1.28 nM. Both the PK and PD characteristics were consistent between the Caucasian and Asian populations. Conclusion The TMDD 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‐C lowering effects between Caucasians and Asians. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303218/pdf |
| Ending Page | 125 |
| Page Count | 12 |
| Starting Page | 114 |
| e-ISSN | 13652125 |
| DOI | 10.1111/bcp.13767 |
| Journal | British journal of clinical pharmacology |
| Issue Number | 1 |
| Volume Number | 85 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2019-01-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: British journal of clinical pharmacology Pharmacokinetic‐pharmacodynamic Monoclonal Antibodies Modelling and Simulation |
| Content Type | Text |
| Resource Type | Article |
