Physiologically based pharmacokinetic modeling of levetiracetam to predict the exposure in hepatic and renal impairment and elderly populations
Abstract Levetiracetam (LEV) is an anti‐epileptic drug approved for use in various populations. The pharmacokinetic (PK) behavior of LEV may be altered in the elderly and patients with renal and hepatic impairment. Thus, dosage adjustment is required. This study was conducted to investigate how the...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-07-01
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| Series: | CPT: Pharmacometrics & Systems Pharmacology |
| Online Access: | https://doi.org/10.1002/psp4.12971 |
| _version_ | 1797780020677050368 |
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| author | Chaozhuang Shen Wenxin Shao Wenhui Wang Hua Sun Xiaohu Wang Kuo Geng Xingwen Wang Haitang Xie |
| author_facet | Chaozhuang Shen Wenxin Shao Wenhui Wang Hua Sun Xiaohu Wang Kuo Geng Xingwen Wang Haitang Xie |
| author_sort | Chaozhuang Shen |
| collection | DOAJ |
| description | Abstract Levetiracetam (LEV) is an anti‐epileptic drug approved for use in various populations. The pharmacokinetic (PK) behavior of LEV may be altered in the elderly and patients with renal and hepatic impairment. Thus, dosage adjustment is required. This study was conducted to investigate how the physiologically‐based PK (PBPK) model describes the PKs of LEV in adult and elderly populations, as well as to predict the PKs of LEV in patients with renal and hepatic impairment in both populations. The whole‐body PBPK models were developed using the reported physicochemical properties of LEV and clinical data. The models were validated using data from clinical studies with different dose ranges and different routes and intervals of administration. The fit performance of the models was assessed by comparing predicted and observed blood concentration data and PK parameters. It is recommended that the doses be reduced to ~70%, 60%, and 45% of the adult dose for the mild, moderate, and severe renal impairment populations and ~95%, 80%, and 57% of the adult dose for the Child Pugh‐A (CP‐A), Child Pugh‐B (CP‐B), and Child Pugh‐C (CP‐C) hepatic impairment populations, respectively. No dose adjustment is required for the healthy elderly population, but dose reduction is required for the elderly with organ dysfunction accordingly, on a scale similar to that of adults. A PBPK model of LEV was successfully developed to optimize dosing regimens for special populations. |
| first_indexed | 2024-03-12T23:37:41Z |
| format | Article |
| id | doaj.art-671b474fb6b643abb41180d53333ea11 |
| institution | Directory Open Access Journal |
| issn | 2163-8306 |
| language | English |
| last_indexed | 2024-03-12T23:37:41Z |
| publishDate | 2023-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | CPT: Pharmacometrics & Systems Pharmacology |
| spelling | doaj.art-671b474fb6b643abb41180d53333ea112023-07-15T04:38:31ZengWileyCPT: Pharmacometrics & Systems Pharmacology2163-83062023-07-011271001101510.1002/psp4.12971Physiologically based pharmacokinetic modeling of levetiracetam to predict the exposure in hepatic and renal impairment and elderly populationsChaozhuang Shen0Wenxin Shao1Wenhui Wang2Hua Sun3Xiaohu Wang4Kuo Geng5Xingwen Wang6Haitang Xie7Anhui Provincial Center for Drug Clinical Evaluation Yijishan Hospital of Wannan Medical College Wuhu Anhui ChinaAnhui Provincial Center for Drug Clinical Evaluation Yijishan Hospital of Wannan Medical College Wuhu Anhui ChinaAnhui Provincial Center for Drug Clinical Evaluation Yijishan Hospital of Wannan Medical College Wuhu Anhui ChinaAnhui Provincial Center for Drug Clinical Evaluation Yijishan Hospital of Wannan Medical College Wuhu Anhui ChinaAnhui Provincial Center for Drug Clinical Evaluation Yijishan Hospital of Wannan Medical College Wuhu Anhui ChinaAnhui Provincial Center for Drug Clinical Evaluation Yijishan Hospital of Wannan Medical College Wuhu Anhui ChinaAnhui Provincial Center for Drug Clinical Evaluation Yijishan Hospital of Wannan Medical College Wuhu Anhui ChinaAnhui Provincial Center for Drug Clinical Evaluation Yijishan Hospital of Wannan Medical College Wuhu Anhui ChinaAbstract Levetiracetam (LEV) is an anti‐epileptic drug approved for use in various populations. The pharmacokinetic (PK) behavior of LEV may be altered in the elderly and patients with renal and hepatic impairment. Thus, dosage adjustment is required. This study was conducted to investigate how the physiologically‐based PK (PBPK) model describes the PKs of LEV in adult and elderly populations, as well as to predict the PKs of LEV in patients with renal and hepatic impairment in both populations. The whole‐body PBPK models were developed using the reported physicochemical properties of LEV and clinical data. The models were validated using data from clinical studies with different dose ranges and different routes and intervals of administration. The fit performance of the models was assessed by comparing predicted and observed blood concentration data and PK parameters. It is recommended that the doses be reduced to ~70%, 60%, and 45% of the adult dose for the mild, moderate, and severe renal impairment populations and ~95%, 80%, and 57% of the adult dose for the Child Pugh‐A (CP‐A), Child Pugh‐B (CP‐B), and Child Pugh‐C (CP‐C) hepatic impairment populations, respectively. No dose adjustment is required for the healthy elderly population, but dose reduction is required for the elderly with organ dysfunction accordingly, on a scale similar to that of adults. A PBPK model of LEV was successfully developed to optimize dosing regimens for special populations.https://doi.org/10.1002/psp4.12971 |
| spellingShingle | Chaozhuang Shen Wenxin Shao Wenhui Wang Hua Sun Xiaohu Wang Kuo Geng Xingwen Wang Haitang Xie Physiologically based pharmacokinetic modeling of levetiracetam to predict the exposure in hepatic and renal impairment and elderly populations CPT: Pharmacometrics & Systems Pharmacology |
| title | Physiologically based pharmacokinetic modeling of levetiracetam to predict the exposure in hepatic and renal impairment and elderly populations |
| title_full | Physiologically based pharmacokinetic modeling of levetiracetam to predict the exposure in hepatic and renal impairment and elderly populations |
| title_fullStr | Physiologically based pharmacokinetic modeling of levetiracetam to predict the exposure in hepatic and renal impairment and elderly populations |
| title_full_unstemmed | Physiologically based pharmacokinetic modeling of levetiracetam to predict the exposure in hepatic and renal impairment and elderly populations |
| title_short | Physiologically based pharmacokinetic modeling of levetiracetam to predict the exposure in hepatic and renal impairment and elderly populations |
| title_sort | physiologically based pharmacokinetic modeling of levetiracetam to predict the exposure in hepatic and renal impairment and elderly populations |
| url | https://doi.org/10.1002/psp4.12971 |
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