A PBPK modeling approach for personalized dose optimization of nicardipine in renal and hepatic dysfunction
Abstract Nicardipine is a calcium channel blocker employed to manage hypertension and angina. It is primarily metabolized in the liver; therefore, hepatic impairment patients may experience drug accumulation, potentially resulting in adverse events. This research aims to design physiologically based...
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Nature Portfolio
2025-06-01
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| Online Access: | https://doi.org/10.1038/s41598-025-03829-4 |
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| author | Ammara Ayub Ammara Zamir Muhammad Fawad Rasool Usman Arshad Faleh Alqahtani |
| author_facet | Ammara Ayub Ammara Zamir Muhammad Fawad Rasool Usman Arshad Faleh Alqahtani |
| author_sort | Ammara Ayub |
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| description | Abstract Nicardipine is a calcium channel blocker employed to manage hypertension and angina. It is primarily metabolized in the liver; therefore, hepatic impairment patients may experience drug accumulation, potentially resulting in adverse events. This research aims to design physiologically based pharmacokinetic (PBPK) model capable of accurately predicting the exposure of nicardipine in healthy individuals as well as hepatic and renal impairment patients. An extensive literature review was conducted to retrieve relevant articles and pharmacokinetic (PK) parameters of nicardipine, for integration into the PK-Sim® program. The modeling approach incepts with the development of healthy PBPK model, which is subsequently extrapolated to diseased populations to assess the alignment of anticipated and reported concentration-time profiles. The precision of the model was then evaluated through visual predictive checks, mean observed–predicted ratios, and average fold error across relevant PK parameters, which adhered to the predefined 2-fold threshold. The observed exposure of nicardipine in Child-Pugh A was found to be ~ 1.5-fold greater than in a healthy population, highlighting the necessity of dosage adjustment in the cirrhotic population. The developed PBPK models have effectively elucidated the PK alterations of nicardipine in healthy and diseased populations, thus the insights gained from these models can inform tailored dosing regimens for enhancing therapeutic efficacy. |
| format | Article |
| id | doaj-art-5cc37a200c29480fb2b7b02b6a705b80 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-5cc37a200c29480fb2b7b02b6a705b802025-08-20T03:10:36ZengNature PortfolioScientific Reports2045-23222025-06-0115111610.1038/s41598-025-03829-4A PBPK modeling approach for personalized dose optimization of nicardipine in renal and hepatic dysfunctionAmmara Ayub0Ammara Zamir1Muhammad Fawad Rasool2Usman Arshad3Faleh Alqahtani4Department of Pharmacy Practice, Faculty of Pharmacy, Bahauddin Zakariya UniversityDepartment of Pharmacy Practice, Faculty of Pharmacy, Bahauddin Zakariya UniversityDepartment of Pharmacy Practice, Faculty of Pharmacy, Bahauddin Zakariya UniversityClinical Pharmacology Modeling and Simulation, GSKDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud UniversityAbstract Nicardipine is a calcium channel blocker employed to manage hypertension and angina. It is primarily metabolized in the liver; therefore, hepatic impairment patients may experience drug accumulation, potentially resulting in adverse events. This research aims to design physiologically based pharmacokinetic (PBPK) model capable of accurately predicting the exposure of nicardipine in healthy individuals as well as hepatic and renal impairment patients. An extensive literature review was conducted to retrieve relevant articles and pharmacokinetic (PK) parameters of nicardipine, for integration into the PK-Sim® program. The modeling approach incepts with the development of healthy PBPK model, which is subsequently extrapolated to diseased populations to assess the alignment of anticipated and reported concentration-time profiles. The precision of the model was then evaluated through visual predictive checks, mean observed–predicted ratios, and average fold error across relevant PK parameters, which adhered to the predefined 2-fold threshold. The observed exposure of nicardipine in Child-Pugh A was found to be ~ 1.5-fold greater than in a healthy population, highlighting the necessity of dosage adjustment in the cirrhotic population. The developed PBPK models have effectively elucidated the PK alterations of nicardipine in healthy and diseased populations, thus the insights gained from these models can inform tailored dosing regimens for enhancing therapeutic efficacy.https://doi.org/10.1038/s41598-025-03829-4NicardipinePBPK modelHypertensionLiver cirrhosisRenal impairment |
| spellingShingle | Ammara Ayub Ammara Zamir Muhammad Fawad Rasool Usman Arshad Faleh Alqahtani A PBPK modeling approach for personalized dose optimization of nicardipine in renal and hepatic dysfunction Scientific Reports Nicardipine PBPK model Hypertension Liver cirrhosis Renal impairment |
| title | A PBPK modeling approach for personalized dose optimization of nicardipine in renal and hepatic dysfunction |
| title_full | A PBPK modeling approach for personalized dose optimization of nicardipine in renal and hepatic dysfunction |
| title_fullStr | A PBPK modeling approach for personalized dose optimization of nicardipine in renal and hepatic dysfunction |
| title_full_unstemmed | A PBPK modeling approach for personalized dose optimization of nicardipine in renal and hepatic dysfunction |
| title_short | A PBPK modeling approach for personalized dose optimization of nicardipine in renal and hepatic dysfunction |
| title_sort | pbpk modeling approach for personalized dose optimization of nicardipine in renal and hepatic dysfunction |
| topic | Nicardipine PBPK model Hypertension Liver cirrhosis Renal impairment |
| url | https://doi.org/10.1038/s41598-025-03829-4 |
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