Optimization of the dosage regimen of zoledronic acid with a kinetic-pharmacodynamic model and exposure-response analysis
Purpose: In order to support the dose optimization of zoledronic acid, the kinetic-pharmacodynamic model and exposure-response analysis were used to describe the changes in bone mineral density in different doses of zoledronic acid and establish the relationship between dose and acute phase reaction...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-09-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1089774/full |
| _version_ | 1797671736116772864 |
|---|---|
| author | Huan Wang Huan Wang Huan Wang Qi Liu Qi Liu Muhan Jiang Muhan Jiang Chunli Song Chunli Song Dongyang Liu Dongyang Liu |
| author_facet | Huan Wang Huan Wang Huan Wang Qi Liu Qi Liu Muhan Jiang Muhan Jiang Chunli Song Chunli Song Dongyang Liu Dongyang Liu |
| author_sort | Huan Wang |
| collection | DOAJ |
| description | Purpose: In order to support the dose optimization of zoledronic acid, the kinetic-pharmacodynamic model and exposure-response analysis were used to describe the changes in bone mineral density in different doses of zoledronic acid and establish the relationship between dose and acute phase reaction.Methods: Data were extracted from literature in accessible public databases. The kinetic-pharmacodynamic model was developed based on the above data using the NONMEM package to estimate parameters describing the relationship between the dose of zoledronic acid and bone mineral density. Exposure-response analysis was developed to establish the relationship between dose and acute phase reaction. Model evaluation was performed using goodness-of-fit, coefficient of variation (CV%). And sensitivity analyses were performed to assess the necessity of related parameters. Then the established model was used to simulate the changes of bone mineral density under different administration regimens, and the literature data was verified.Results: The kinetic-pharmacodynamic model successfully described zoledronic acid dose and change of bone mineral density in osteoporosis patients, with coefficient of variation of most less than 71.5%. The exposure-response analysis showed the incidence of acute phase reaction is dose-dependent. The bone mineral density was simulated based on the developed kinetic-pharmacodynamic model. And the simulated change of bone mineral density and the incidence of acute phase reaction could be helpful to propose a dosage regimen.Conclusion: Overall, the kinetic-pharmacodynamic model described changes of bone mineral density in different doses of zoledronic acid in vivo. And, the model and the exposure-response analysis also showed to provide the assessment of dose-response relationship for zoledronic acid. |
| first_indexed | 2024-03-11T21:19:52Z |
| format | Article |
| id | doaj.art-5830021e478b4e6198b0dadf159fc5c5 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-11T21:19:52Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-5830021e478b4e6198b0dadf159fc5c52023-09-28T09:29:09ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-09-011410.3389/fphar.2023.10897741089774Optimization of the dosage regimen of zoledronic acid with a kinetic-pharmacodynamic model and exposure-response analysisHuan Wang0Huan Wang1Huan Wang2Qi Liu3Qi Liu4Muhan Jiang5Muhan Jiang6Chunli Song7Chunli Song8Dongyang Liu9Dongyang Liu10Department of Orthopedics, Peking University Third Hospital, Beijing, ChinaDrug Clinical Trial Center, Peking University Third Hospital, Beijing, ChinaCenter of Clinical Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital Beijing, Beijing, ChinaDrug Clinical Trial Center, Peking University Third Hospital, Beijing, ChinaCenter of Clinical Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital Beijing, Beijing, ChinaDrug Clinical Trial Center, Peking University Third Hospital, Beijing, ChinaCenter of Clinical Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital Beijing, Beijing, ChinaDepartment of Orthopedics, Peking University Third Hospital, Beijing, ChinaCenter of Clinical Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital Beijing, Beijing, ChinaDrug Clinical Trial Center, Peking University Third Hospital, Beijing, ChinaCenter of Clinical Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital Beijing, Beijing, ChinaPurpose: In order to support the dose optimization of zoledronic acid, the kinetic-pharmacodynamic model and exposure-response analysis were used to describe the changes in bone mineral density in different doses of zoledronic acid and establish the relationship between dose and acute phase reaction.Methods: Data were extracted from literature in accessible public databases. The kinetic-pharmacodynamic model was developed based on the above data using the NONMEM package to estimate parameters describing the relationship between the dose of zoledronic acid and bone mineral density. Exposure-response analysis was developed to establish the relationship between dose and acute phase reaction. Model evaluation was performed using goodness-of-fit, coefficient of variation (CV%). And sensitivity analyses were performed to assess the necessity of related parameters. Then the established model was used to simulate the changes of bone mineral density under different administration regimens, and the literature data was verified.Results: The kinetic-pharmacodynamic model successfully described zoledronic acid dose and change of bone mineral density in osteoporosis patients, with coefficient of variation of most less than 71.5%. The exposure-response analysis showed the incidence of acute phase reaction is dose-dependent. The bone mineral density was simulated based on the developed kinetic-pharmacodynamic model. And the simulated change of bone mineral density and the incidence of acute phase reaction could be helpful to propose a dosage regimen.Conclusion: Overall, the kinetic-pharmacodynamic model described changes of bone mineral density in different doses of zoledronic acid in vivo. And, the model and the exposure-response analysis also showed to provide the assessment of dose-response relationship for zoledronic acid.https://www.frontiersin.org/articles/10.3389/fphar.2023.1089774/fullzoledronic acidosteoporosisdosing regimenkinetic-pharmacodynamic modelexposure-response analysis |
| spellingShingle | Huan Wang Huan Wang Huan Wang Qi Liu Qi Liu Muhan Jiang Muhan Jiang Chunli Song Chunli Song Dongyang Liu Dongyang Liu Optimization of the dosage regimen of zoledronic acid with a kinetic-pharmacodynamic model and exposure-response analysis Frontiers in Pharmacology zoledronic acid osteoporosis dosing regimen kinetic-pharmacodynamic model exposure-response analysis |
| title | Optimization of the dosage regimen of zoledronic acid with a kinetic-pharmacodynamic model and exposure-response analysis |
| title_full | Optimization of the dosage regimen of zoledronic acid with a kinetic-pharmacodynamic model and exposure-response analysis |
| title_fullStr | Optimization of the dosage regimen of zoledronic acid with a kinetic-pharmacodynamic model and exposure-response analysis |
| title_full_unstemmed | Optimization of the dosage regimen of zoledronic acid with a kinetic-pharmacodynamic model and exposure-response analysis |
| title_short | Optimization of the dosage regimen of zoledronic acid with a kinetic-pharmacodynamic model and exposure-response analysis |
| title_sort | optimization of the dosage regimen of zoledronic acid with a kinetic pharmacodynamic model and exposure response analysis |
| topic | zoledronic acid osteoporosis dosing regimen kinetic-pharmacodynamic model exposure-response analysis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1089774/full |
| work_keys_str_mv | AT huanwang optimizationofthedosageregimenofzoledronicacidwithakineticpharmacodynamicmodelandexposureresponseanalysis AT huanwang optimizationofthedosageregimenofzoledronicacidwithakineticpharmacodynamicmodelandexposureresponseanalysis AT huanwang optimizationofthedosageregimenofzoledronicacidwithakineticpharmacodynamicmodelandexposureresponseanalysis AT qiliu optimizationofthedosageregimenofzoledronicacidwithakineticpharmacodynamicmodelandexposureresponseanalysis AT qiliu optimizationofthedosageregimenofzoledronicacidwithakineticpharmacodynamicmodelandexposureresponseanalysis AT muhanjiang optimizationofthedosageregimenofzoledronicacidwithakineticpharmacodynamicmodelandexposureresponseanalysis AT muhanjiang optimizationofthedosageregimenofzoledronicacidwithakineticpharmacodynamicmodelandexposureresponseanalysis AT chunlisong optimizationofthedosageregimenofzoledronicacidwithakineticpharmacodynamicmodelandexposureresponseanalysis AT chunlisong optimizationofthedosageregimenofzoledronicacidwithakineticpharmacodynamicmodelandexposureresponseanalysis AT dongyangliu optimizationofthedosageregimenofzoledronicacidwithakineticpharmacodynamicmodelandexposureresponseanalysis AT dongyangliu optimizationofthedosageregimenofzoledronicacidwithakineticpharmacodynamicmodelandexposureresponseanalysis |