Application of a physiologically based pharmacokinetic model in predicting captopril disposition in children with chronic kidney disease
Abstract Over the last several decades, angiotensin-converting enzyme inhibitors (ACEIs) have been a staple in the treatment of hypertension and renovascular disorders in children. One of the ACEIs, captopril, is projected to have all the benefits of traditional vasodilators. However, conducting cli...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-29798-0 |
| _version_ | 1797864781983514624 |
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| author | Sundus Khalid Muhammad Fawad Rasool Imran Masood Imran Imran Hamid Saeed Tanveer Ahmad Nawaf Shalih Alqahtani Fahad Ali Alshammari Faleh Alqahtani |
| author_facet | Sundus Khalid Muhammad Fawad Rasool Imran Masood Imran Imran Hamid Saeed Tanveer Ahmad Nawaf Shalih Alqahtani Fahad Ali Alshammari Faleh Alqahtani |
| author_sort | Sundus Khalid |
| collection | DOAJ |
| description | Abstract Over the last several decades, angiotensin-converting enzyme inhibitors (ACEIs) have been a staple in the treatment of hypertension and renovascular disorders in children. One of the ACEIs, captopril, is projected to have all the benefits of traditional vasodilators. However, conducting clinical trials for determining the pharmacokinetics (PK) of a drug is challenging, particularly in pediatrics. As a result, modeling and simulation methods have been developed to identify the safe and effective dosages of drugs. The physiologically based pharmacokinetic (PBPK) modeling is a well-established method that permits extrapolation from adult to juvenile populations. By using SIMCYP simulator, as a modeling platform, a previously developed PBPK drug-disease model of captopril was scaled to renally impaired pediatrics population for predicting captopril PK. The visual predictive checks, predicted/observed ratios (ratiopred/obs), and the average fold error of PK parameters were used for model evaluation. The model predictions were comparable with the reported PK data of captopril in mild and severe chronic kidney disease (CKD) patients, as the mean ratiopred/obs Cmax and AUC0−t were 1.44 (95% CI 1.07 − 1.80) and 1.26 (95% CI 0.93 − 1.59), respectively. The successfully developed captopril-CKD pediatric model can be used in suggesting drug dosing in children diagnosed with different stages of CKD. |
| first_indexed | 2024-04-09T22:57:49Z |
| format | Article |
| id | doaj.art-e3ea07c3b6714489bb7bb2825cecc935 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T22:57:49Z |
| publishDate | 2023-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-e3ea07c3b6714489bb7bb2825cecc9352023-03-22T11:11:36ZengNature PortfolioScientific Reports2045-23222023-02-0113111010.1038/s41598-023-29798-0Application of a physiologically based pharmacokinetic model in predicting captopril disposition in children with chronic kidney diseaseSundus Khalid0Muhammad Fawad Rasool1Imran Masood2Imran Imran3Hamid Saeed4Tanveer Ahmad5Nawaf Shalih Alqahtani6Fahad Ali Alshammari7Faleh Alqahtani8Department of Pharmacy Practice, Faculty of Pharmacy, Bahauddin Zakariya UniversityDepartment of Pharmacy Practice, Faculty of Pharmacy, Bahauddin Zakariya UniversityDepartment of Pharmacy Practice, Faculty of Pharmacy, The Islamia University of BahawalpurDepartment of Pharmacology, Faculty of Pharmacy, Bahauddin Zakariya UniversitySection of Pharmaceutics, University College of Pharmacy, Allama Iqbal Campus, University of the PunjabInstitute for Advanced Biosciences (IAB), CNRS UMR5309, INSERM U1209, Grenoble Alpes UniversityDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud UniversityDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud UniversityDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud UniversityAbstract Over the last several decades, angiotensin-converting enzyme inhibitors (ACEIs) have been a staple in the treatment of hypertension and renovascular disorders in children. One of the ACEIs, captopril, is projected to have all the benefits of traditional vasodilators. However, conducting clinical trials for determining the pharmacokinetics (PK) of a drug is challenging, particularly in pediatrics. As a result, modeling and simulation methods have been developed to identify the safe and effective dosages of drugs. The physiologically based pharmacokinetic (PBPK) modeling is a well-established method that permits extrapolation from adult to juvenile populations. By using SIMCYP simulator, as a modeling platform, a previously developed PBPK drug-disease model of captopril was scaled to renally impaired pediatrics population for predicting captopril PK. The visual predictive checks, predicted/observed ratios (ratiopred/obs), and the average fold error of PK parameters were used for model evaluation. The model predictions were comparable with the reported PK data of captopril in mild and severe chronic kidney disease (CKD) patients, as the mean ratiopred/obs Cmax and AUC0−t were 1.44 (95% CI 1.07 − 1.80) and 1.26 (95% CI 0.93 − 1.59), respectively. The successfully developed captopril-CKD pediatric model can be used in suggesting drug dosing in children diagnosed with different stages of CKD.https://doi.org/10.1038/s41598-023-29798-0 |
| spellingShingle | Sundus Khalid Muhammad Fawad Rasool Imran Masood Imran Imran Hamid Saeed Tanveer Ahmad Nawaf Shalih Alqahtani Fahad Ali Alshammari Faleh Alqahtani Application of a physiologically based pharmacokinetic model in predicting captopril disposition in children with chronic kidney disease Scientific Reports |
| title | Application of a physiologically based pharmacokinetic model in predicting captopril disposition in children with chronic kidney disease |
| title_full | Application of a physiologically based pharmacokinetic model in predicting captopril disposition in children with chronic kidney disease |
| title_fullStr | Application of a physiologically based pharmacokinetic model in predicting captopril disposition in children with chronic kidney disease |
| title_full_unstemmed | Application of a physiologically based pharmacokinetic model in predicting captopril disposition in children with chronic kidney disease |
| title_short | Application of a physiologically based pharmacokinetic model in predicting captopril disposition in children with chronic kidney disease |
| title_sort | application of a physiologically based pharmacokinetic model in predicting captopril disposition in children with chronic kidney disease |
| url | https://doi.org/10.1038/s41598-023-29798-0 |
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