Physiologically based pharmacokinetic modeling of daptomycin dose optimization in pediatric patients with renal impairment
Background and Objective: Daptomycin is used to treat Gram-positive infections in adults and children and its dosing varies among different age groups. We focused on the pharmacokinetics of daptomycin in children with renal impairment, which has not been evaluated.Methods: A physiologically based ph...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-08-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.838599/full |
| _version_ | 1811321390197899264 |
|---|---|
| author | Lingling Ye Xiang You Jie Zhou Chaohui Wu Meng Ke Wanhong Wu Pinfang Huang Cuihong Lin |
| author_facet | Lingling Ye Xiang You Jie Zhou Chaohui Wu Meng Ke Wanhong Wu Pinfang Huang Cuihong Lin |
| author_sort | Lingling Ye |
| collection | DOAJ |
| description | Background and Objective: Daptomycin is used to treat Gram-positive infections in adults and children and its dosing varies among different age groups. We focused on the pharmacokinetics of daptomycin in children with renal impairment, which has not been evaluated.Methods: A physiologically based pharmacokinetic (PBPK) model of daptomycin was established and validated to simulate its disposition in healthy populations and adults with renal impairment, along with a daptomycin exposure simulated in pediatric patients with renal impairment.Results: The simulated PBPK modeling results for various regimens of intravenously administered daptomycin were consistent with observed data according to the fold error below the threshold of 2. The Cmax and AUC of daptomycin did not differ significantly between children with mild-to-moderate renal impairment and healthy children. The AUC increased by an average of 1.55-fold and 1.85-fold in severe renal impairment and end-stage renal disease, respectively. The changes were more significant in younger children and could reach a more than 2-fold change. This scenario necessitates further daptomycin dose adjustments.Conclusion: Dose adjustments take into account the efficacy and safety of the drug; however, the steady-state Cmin of daptomycin may be above 24.3 mg/L in a few instances. We recommend monitoring creatine phosphokinase more than once a week when using daptomycin in children with renal impairment. |
| first_indexed | 2024-04-13T13:15:53Z |
| format | Article |
| id | doaj.art-0fbb0c08063e441fba0f8068487c190a |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-13T13:15:53Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-0fbb0c08063e441fba0f8068487c190a2022-12-22T02:45:27ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-08-011310.3389/fphar.2022.838599838599Physiologically based pharmacokinetic modeling of daptomycin dose optimization in pediatric patients with renal impairmentLingling YeXiang YouJie ZhouChaohui WuMeng KeWanhong WuPinfang HuangCuihong LinBackground and Objective: Daptomycin is used to treat Gram-positive infections in adults and children and its dosing varies among different age groups. We focused on the pharmacokinetics of daptomycin in children with renal impairment, which has not been evaluated.Methods: A physiologically based pharmacokinetic (PBPK) model of daptomycin was established and validated to simulate its disposition in healthy populations and adults with renal impairment, along with a daptomycin exposure simulated in pediatric patients with renal impairment.Results: The simulated PBPK modeling results for various regimens of intravenously administered daptomycin were consistent with observed data according to the fold error below the threshold of 2. The Cmax and AUC of daptomycin did not differ significantly between children with mild-to-moderate renal impairment and healthy children. The AUC increased by an average of 1.55-fold and 1.85-fold in severe renal impairment and end-stage renal disease, respectively. The changes were more significant in younger children and could reach a more than 2-fold change. This scenario necessitates further daptomycin dose adjustments.Conclusion: Dose adjustments take into account the efficacy and safety of the drug; however, the steady-state Cmin of daptomycin may be above 24.3 mg/L in a few instances. We recommend monitoring creatine phosphokinase more than once a week when using daptomycin in children with renal impairment.https://www.frontiersin.org/articles/10.3389/fphar.2022.838599/fulldaptomycinphysiologically based pharmacokinetic modelpediatric patients with renal impairmentpharmacokineticspharmacodynamics |
| spellingShingle | Lingling Ye Xiang You Jie Zhou Chaohui Wu Meng Ke Wanhong Wu Pinfang Huang Cuihong Lin Physiologically based pharmacokinetic modeling of daptomycin dose optimization in pediatric patients with renal impairment Frontiers in Pharmacology daptomycin physiologically based pharmacokinetic model pediatric patients with renal impairment pharmacokinetics pharmacodynamics |
| title | Physiologically based pharmacokinetic modeling of daptomycin dose optimization in pediatric patients with renal impairment |
| title_full | Physiologically based pharmacokinetic modeling of daptomycin dose optimization in pediatric patients with renal impairment |
| title_fullStr | Physiologically based pharmacokinetic modeling of daptomycin dose optimization in pediatric patients with renal impairment |
| title_full_unstemmed | Physiologically based pharmacokinetic modeling of daptomycin dose optimization in pediatric patients with renal impairment |
| title_short | Physiologically based pharmacokinetic modeling of daptomycin dose optimization in pediatric patients with renal impairment |
| title_sort | physiologically based pharmacokinetic modeling of daptomycin dose optimization in pediatric patients with renal impairment |
| topic | daptomycin physiologically based pharmacokinetic model pediatric patients with renal impairment pharmacokinetics pharmacodynamics |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.838599/full |
| work_keys_str_mv | AT linglingye physiologicallybasedpharmacokineticmodelingofdaptomycindoseoptimizationinpediatricpatientswithrenalimpairment AT xiangyou physiologicallybasedpharmacokineticmodelingofdaptomycindoseoptimizationinpediatricpatientswithrenalimpairment AT jiezhou physiologicallybasedpharmacokineticmodelingofdaptomycindoseoptimizationinpediatricpatientswithrenalimpairment AT chaohuiwu physiologicallybasedpharmacokineticmodelingofdaptomycindoseoptimizationinpediatricpatientswithrenalimpairment AT mengke physiologicallybasedpharmacokineticmodelingofdaptomycindoseoptimizationinpediatricpatientswithrenalimpairment AT wanhongwu physiologicallybasedpharmacokineticmodelingofdaptomycindoseoptimizationinpediatricpatientswithrenalimpairment AT pinfanghuang physiologicallybasedpharmacokineticmodelingofdaptomycindoseoptimizationinpediatricpatientswithrenalimpairment AT cuihonglin physiologicallybasedpharmacokineticmodelingofdaptomycindoseoptimizationinpediatricpatientswithrenalimpairment |