Model‐based meta‐analysis of ethnic differences and their variabilities in clearance of oral drugs classified by clearance mechanism
Abstract In this study, the ethnic ratios (ERs) of oral clearance between Japanese and Western populations were subjected to model‐based meta‐analysis (MBMA) for 81 drugs evaluated in 673 clinical studies. The drugs were classified into eight groups according to the clearance mechanism, and the ER f...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-08-01
|
| Series: | CPT: Pharmacometrics & Systems Pharmacology |
| Online Access: | https://doi.org/10.1002/psp4.12980 |
| _version_ | 1797742344896774144 |
|---|---|
| author | Hiromi Sato Rika Marutani Ryota Takaoka Daniel Mori‐Fegan Xinying Wang Kazuya Maeda Hiroyuki Kusuhara Hiroshi Suzuki Hideki Yoshioka Akihiro Hisaka |
| author_facet | Hiromi Sato Rika Marutani Ryota Takaoka Daniel Mori‐Fegan Xinying Wang Kazuya Maeda Hiroyuki Kusuhara Hiroshi Suzuki Hideki Yoshioka Akihiro Hisaka |
| author_sort | Hiromi Sato |
| collection | DOAJ |
| description | Abstract In this study, the ethnic ratios (ERs) of oral clearance between Japanese and Western populations were subjected to model‐based meta‐analysis (MBMA) for 81 drugs evaluated in 673 clinical studies. The drugs were classified into eight groups according to the clearance mechanism, and the ER for each group was inferred together with interindividual variability (IIV), interstudy variability (ISV), and inter‐drug variability within a group (IDV) using the Markov chain Monte Carlo (MCMC) method. The ER, IIV, ISV, and IDV were dependent on the clearance mechanism, and, except for particular groups such as drugs metabolized by polymorphic enzymes or their clearance mechanism is not confirmative, the ethnic difference was found to be generally small. The IIV was well‐matched across ethnicities, and the ISV was approximately half of the IIV as the coefficient of variation. To adequately assess ethnic differences in oral clearance without false detections, phase I studies should be designed with full consideration of the mechanism of clearance. This study suggests that the methodology of classifying drugs based on the mechanism that causes ethnic differences and performing MBMA with statistical techniques such as MCMC analysis is helpful for a rational understanding of ethnic differences and for strategic drug development. |
| first_indexed | 2024-03-12T14:39:30Z |
| format | Article |
| id | doaj.art-cfa892f66523407c90c434d60454df47 |
| institution | Directory Open Access Journal |
| issn | 2163-8306 |
| language | English |
| last_indexed | 2024-03-12T14:39:30Z |
| publishDate | 2023-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | CPT: Pharmacometrics & Systems Pharmacology |
| spelling | doaj.art-cfa892f66523407c90c434d60454df472023-08-16T15:38:05ZengWileyCPT: Pharmacometrics & Systems Pharmacology2163-83062023-08-011281132114210.1002/psp4.12980Model‐based meta‐analysis of ethnic differences and their variabilities in clearance of oral drugs classified by clearance mechanismHiromi Sato0Rika Marutani1Ryota Takaoka2Daniel Mori‐Fegan3Xinying Wang4Kazuya Maeda5Hiroyuki Kusuhara6Hiroshi Suzuki7Hideki Yoshioka8Akihiro Hisaka9Laboratory of Clinical Pharmacology and Pharmacometrics, Graduate School of Pharmaceutical Sciences Chiba University Chiba JapanThe University of Tokyo Hospital Tokyo JapanLaboratory of Clinical Pharmacology and Pharmacometrics, Graduate School of Pharmaceutical Sciences Chiba University Chiba JapanLaboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences The University of Tokyo Tokyo JapanLaboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences The University of Tokyo Tokyo JapanLaboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences The University of Tokyo Tokyo JapanLaboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences The University of Tokyo Tokyo JapanThe University of Tokyo Hospital Tokyo JapanLaboratory of Clinical Pharmacology and Pharmacometrics, Graduate School of Pharmaceutical Sciences Chiba University Chiba JapanLaboratory of Clinical Pharmacology and Pharmacometrics, Graduate School of Pharmaceutical Sciences Chiba University Chiba JapanAbstract In this study, the ethnic ratios (ERs) of oral clearance between Japanese and Western populations were subjected to model‐based meta‐analysis (MBMA) for 81 drugs evaluated in 673 clinical studies. The drugs were classified into eight groups according to the clearance mechanism, and the ER for each group was inferred together with interindividual variability (IIV), interstudy variability (ISV), and inter‐drug variability within a group (IDV) using the Markov chain Monte Carlo (MCMC) method. The ER, IIV, ISV, and IDV were dependent on the clearance mechanism, and, except for particular groups such as drugs metabolized by polymorphic enzymes or their clearance mechanism is not confirmative, the ethnic difference was found to be generally small. The IIV was well‐matched across ethnicities, and the ISV was approximately half of the IIV as the coefficient of variation. To adequately assess ethnic differences in oral clearance without false detections, phase I studies should be designed with full consideration of the mechanism of clearance. This study suggests that the methodology of classifying drugs based on the mechanism that causes ethnic differences and performing MBMA with statistical techniques such as MCMC analysis is helpful for a rational understanding of ethnic differences and for strategic drug development.https://doi.org/10.1002/psp4.12980 |
| spellingShingle | Hiromi Sato Rika Marutani Ryota Takaoka Daniel Mori‐Fegan Xinying Wang Kazuya Maeda Hiroyuki Kusuhara Hiroshi Suzuki Hideki Yoshioka Akihiro Hisaka Model‐based meta‐analysis of ethnic differences and their variabilities in clearance of oral drugs classified by clearance mechanism CPT: Pharmacometrics & Systems Pharmacology |
| title | Model‐based meta‐analysis of ethnic differences and their variabilities in clearance of oral drugs classified by clearance mechanism |
| title_full | Model‐based meta‐analysis of ethnic differences and their variabilities in clearance of oral drugs classified by clearance mechanism |
| title_fullStr | Model‐based meta‐analysis of ethnic differences and their variabilities in clearance of oral drugs classified by clearance mechanism |
| title_full_unstemmed | Model‐based meta‐analysis of ethnic differences and their variabilities in clearance of oral drugs classified by clearance mechanism |
| title_short | Model‐based meta‐analysis of ethnic differences and their variabilities in clearance of oral drugs classified by clearance mechanism |
| title_sort | model based meta analysis of ethnic differences and their variabilities in clearance of oral drugs classified by clearance mechanism |
| url | https://doi.org/10.1002/psp4.12980 |
| work_keys_str_mv | AT hiromisato modelbasedmetaanalysisofethnicdifferencesandtheirvariabilitiesinclearanceoforaldrugsclassifiedbyclearancemechanism AT rikamarutani modelbasedmetaanalysisofethnicdifferencesandtheirvariabilitiesinclearanceoforaldrugsclassifiedbyclearancemechanism AT ryotatakaoka modelbasedmetaanalysisofethnicdifferencesandtheirvariabilitiesinclearanceoforaldrugsclassifiedbyclearancemechanism AT danielmorifegan modelbasedmetaanalysisofethnicdifferencesandtheirvariabilitiesinclearanceoforaldrugsclassifiedbyclearancemechanism AT xinyingwang modelbasedmetaanalysisofethnicdifferencesandtheirvariabilitiesinclearanceoforaldrugsclassifiedbyclearancemechanism AT kazuyamaeda modelbasedmetaanalysisofethnicdifferencesandtheirvariabilitiesinclearanceoforaldrugsclassifiedbyclearancemechanism AT hiroyukikusuhara modelbasedmetaanalysisofethnicdifferencesandtheirvariabilitiesinclearanceoforaldrugsclassifiedbyclearancemechanism AT hiroshisuzuki modelbasedmetaanalysisofethnicdifferencesandtheirvariabilitiesinclearanceoforaldrugsclassifiedbyclearancemechanism AT hidekiyoshioka modelbasedmetaanalysisofethnicdifferencesandtheirvariabilitiesinclearanceoforaldrugsclassifiedbyclearancemechanism AT akihirohisaka modelbasedmetaanalysisofethnicdifferencesandtheirvariabilitiesinclearanceoforaldrugsclassifiedbyclearancemechanism |