The pharmacokinetic-pharmacodynamic model of azithromycin for lipopolysaccharide-induced depressive-like behavior in mice.
A mechanism-based model was developed to describe the time course of lipopolysaccharide-induced depressive-like behavior and azithromycin pharmacodynamics in mice. The lipopolysaccharide-induced disease progression was monitored by lipopolysaccharide, proinflammatory cytokines, and kynrenine concent...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3554664?pdf=render |
| _version_ | 1818179634717523968 |
|---|---|
| author | Kun Hao Qu Qi Haiping Hao Guangji Wang Yuancheng Chen Yan Liang Lin Xie |
| author_facet | Kun Hao Qu Qi Haiping Hao Guangji Wang Yuancheng Chen Yan Liang Lin Xie |
| author_sort | Kun Hao |
| collection | DOAJ |
| description | A mechanism-based model was developed to describe the time course of lipopolysaccharide-induced depressive-like behavior and azithromycin pharmacodynamics in mice. The lipopolysaccharide-induced disease progression was monitored by lipopolysaccharide, proinflammatory cytokines, and kynrenine concentration in plasma. The depressive-like behavior was investigated by forced swimming test and tail suspension test. Azithromycin was selected to inhibit the surge of proinflammatory cytokines induced by lipopolysaccharide. Disease progression model and azithromycin pharmacodynamics were constructed from transduction and indirect response models. A delay in the onset of increased proinflammatory cytokines, kynrenine, and behavior test compared to lipopolysaccharide was successfully characterized by series transduction models. The inhibition of azithromycin on proinflammatory cytokines was described by an indirect response model. After lipopolysaccharide challenging, the proinflammatory cytokines, kynrenine and behavior tests would peak approximately at 3, 12, and 24 h respectively, and then the time courses slowly declined toward a baseline state after peak response. During azithromycin administration, the peak levels of proinflammatory cytokines, kynrenine and behavior indexes decreased. Model parameters indicated that azithromycin significantly inhibited the proinflammatory cytokines level in plasma and improved the depressive-like behavior induced by inflammation. The integrated model for disease progression and drug intervention captures turnovers of proinflammatory cytokines, kynrenine and the behavior results in the different time phases and conditions. |
| first_indexed | 2024-12-11T21:07:00Z |
| format | Article |
| id | doaj.art-a6224572517e44f28dd987b24dd3eda5 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T21:07:00Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a6224572517e44f28dd987b24dd3eda52022-12-22T00:50:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e5498110.1371/journal.pone.0054981The pharmacokinetic-pharmacodynamic model of azithromycin for lipopolysaccharide-induced depressive-like behavior in mice.Kun HaoQu QiHaiping HaoGuangji WangYuancheng ChenYan LiangLin XieA mechanism-based model was developed to describe the time course of lipopolysaccharide-induced depressive-like behavior and azithromycin pharmacodynamics in mice. The lipopolysaccharide-induced disease progression was monitored by lipopolysaccharide, proinflammatory cytokines, and kynrenine concentration in plasma. The depressive-like behavior was investigated by forced swimming test and tail suspension test. Azithromycin was selected to inhibit the surge of proinflammatory cytokines induced by lipopolysaccharide. Disease progression model and azithromycin pharmacodynamics were constructed from transduction and indirect response models. A delay in the onset of increased proinflammatory cytokines, kynrenine, and behavior test compared to lipopolysaccharide was successfully characterized by series transduction models. The inhibition of azithromycin on proinflammatory cytokines was described by an indirect response model. After lipopolysaccharide challenging, the proinflammatory cytokines, kynrenine and behavior tests would peak approximately at 3, 12, and 24 h respectively, and then the time courses slowly declined toward a baseline state after peak response. During azithromycin administration, the peak levels of proinflammatory cytokines, kynrenine and behavior indexes decreased. Model parameters indicated that azithromycin significantly inhibited the proinflammatory cytokines level in plasma and improved the depressive-like behavior induced by inflammation. The integrated model for disease progression and drug intervention captures turnovers of proinflammatory cytokines, kynrenine and the behavior results in the different time phases and conditions.http://europepmc.org/articles/PMC3554664?pdf=render |
| spellingShingle | Kun Hao Qu Qi Haiping Hao Guangji Wang Yuancheng Chen Yan Liang Lin Xie The pharmacokinetic-pharmacodynamic model of azithromycin for lipopolysaccharide-induced depressive-like behavior in mice. PLoS ONE |
| title | The pharmacokinetic-pharmacodynamic model of azithromycin for lipopolysaccharide-induced depressive-like behavior in mice. |
| title_full | The pharmacokinetic-pharmacodynamic model of azithromycin for lipopolysaccharide-induced depressive-like behavior in mice. |
| title_fullStr | The pharmacokinetic-pharmacodynamic model of azithromycin for lipopolysaccharide-induced depressive-like behavior in mice. |
| title_full_unstemmed | The pharmacokinetic-pharmacodynamic model of azithromycin for lipopolysaccharide-induced depressive-like behavior in mice. |
| title_short | The pharmacokinetic-pharmacodynamic model of azithromycin for lipopolysaccharide-induced depressive-like behavior in mice. |
| title_sort | pharmacokinetic pharmacodynamic model of azithromycin for lipopolysaccharide induced depressive like behavior in mice |
| url | http://europepmc.org/articles/PMC3554664?pdf=render |
| work_keys_str_mv | AT kunhao thepharmacokineticpharmacodynamicmodelofazithromycinforlipopolysaccharideinduceddepressivelikebehaviorinmice AT quqi thepharmacokineticpharmacodynamicmodelofazithromycinforlipopolysaccharideinduceddepressivelikebehaviorinmice AT haipinghao thepharmacokineticpharmacodynamicmodelofazithromycinforlipopolysaccharideinduceddepressivelikebehaviorinmice AT guangjiwang thepharmacokineticpharmacodynamicmodelofazithromycinforlipopolysaccharideinduceddepressivelikebehaviorinmice AT yuanchengchen thepharmacokineticpharmacodynamicmodelofazithromycinforlipopolysaccharideinduceddepressivelikebehaviorinmice AT yanliang thepharmacokineticpharmacodynamicmodelofazithromycinforlipopolysaccharideinduceddepressivelikebehaviorinmice AT linxie thepharmacokineticpharmacodynamicmodelofazithromycinforlipopolysaccharideinduceddepressivelikebehaviorinmice AT kunhao pharmacokineticpharmacodynamicmodelofazithromycinforlipopolysaccharideinduceddepressivelikebehaviorinmice AT quqi pharmacokineticpharmacodynamicmodelofazithromycinforlipopolysaccharideinduceddepressivelikebehaviorinmice AT haipinghao pharmacokineticpharmacodynamicmodelofazithromycinforlipopolysaccharideinduceddepressivelikebehaviorinmice AT guangjiwang pharmacokineticpharmacodynamicmodelofazithromycinforlipopolysaccharideinduceddepressivelikebehaviorinmice AT yuanchengchen pharmacokineticpharmacodynamicmodelofazithromycinforlipopolysaccharideinduceddepressivelikebehaviorinmice AT yanliang pharmacokineticpharmacodynamicmodelofazithromycinforlipopolysaccharideinduceddepressivelikebehaviorinmice AT linxie pharmacokineticpharmacodynamicmodelofazithromycinforlipopolysaccharideinduceddepressivelikebehaviorinmice |