Pharmacokinetics and exposure–safety relationship of ciprofol for sedation in mechanically ventilated patients in the intensive care unit
Abstract Ciprofol (HSK3486) is a newly developed, highly selective γ‐aminobutyric acid‐A (GABAA) receptor potentiator that is recently approved for a new indication of sedation for patients in the intensive care unit (ICU) in China. This analysis aimed to characterize the population pharmacokinetics...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-05-01
|
| Series: | CPT: Pharmacometrics & Systems Pharmacology |
| Online Access: | https://doi.org/10.1002/psp4.13121 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849421468060876800 |
|---|---|
| author | Lu Liu Kun Wang Zhongyi Sun Pangke Yan Mengyue Hu Xiao Liu Meixia Chen Nan Wu Xiaoqiang Xiang |
| author_facet | Lu Liu Kun Wang Zhongyi Sun Pangke Yan Mengyue Hu Xiao Liu Meixia Chen Nan Wu Xiaoqiang Xiang |
| author_sort | Lu Liu |
| collection | DOAJ |
| description | Abstract Ciprofol (HSK3486) is a newly developed, highly selective γ‐aminobutyric acid‐A (GABAA) receptor potentiator that is recently approved for a new indication of sedation for patients in the intensive care unit (ICU) in China. This analysis aimed to characterize the population pharmacokinetics (PopPKs) of ciprofol and evaluate the relationship of exposure with hypotension in mechanically ventilated patients in the ICU. A total of 462 subjects with 3918 concentration measurements from two clinical trials of mechanically ventilated patients in the ICU, four clinical trials of elective surgical patients, and six clinical trials of healthy subjects were used in the PopPK analysis. Exposure–safety relationship for hypotension was evaluated based on the data gathered from 112 subjects in two clinical trials of mechanically ventilated patients in the ICU. Ciprofol pharmacokinetics (PKs) was adequately described by a three‐compartment linear disposition model with first‐order elimination. Body weight, age, sex, blood sampling site (vein vs. arterial), study design (long‐term infusion vs. short‐term infusion), and patient population (ICU vs. non‐ICU) were identified as statistically significant covariates on the PKs of ciprofol. Within the exposure range of the mechanically ventilated ICU patient population, no meaningful association was observed between ciprofol exposure and the incidence of hypotension. These results support the dosing regimen currently used in mechanically ventilated patients in the ICU. |
| format | Article |
| id | doaj-art-386fd64f97e8421bbd3f8ade6063e13d |
| institution | Kabale University |
| issn | 2163-8306 |
| language | English |
| publishDate | 2024-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | CPT: Pharmacometrics & Systems Pharmacology |
| spelling | doaj-art-386fd64f97e8421bbd3f8ade6063e13d2025-08-20T03:31:27ZengWileyCPT: Pharmacometrics & Systems Pharmacology2163-83062024-05-0113582383610.1002/psp4.13121Pharmacokinetics and exposure–safety relationship of ciprofol for sedation in mechanically ventilated patients in the intensive care unitLu Liu0Kun Wang1Zhongyi Sun2Pangke Yan3Mengyue Hu4Xiao Liu5Meixia Chen6Nan Wu7Xiaoqiang Xiang8Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy Fudan University Shanghai ChinaShanghai Qiangshi Information Technology Co., Ltd. Shanghai ChinaShanghai Qiangshi Information Technology Co., Ltd. Shanghai ChinaHaisco Pharmaceutical Group Co. Ltd. Chengdu ChinaHaisco Pharmaceutical Group Co. Ltd. Chengdu ChinaHaisco Pharmaceutical Group Co. Ltd. Chengdu ChinaHaisco Pharmaceutical Group Co. Ltd. Chengdu ChinaHaisco Pharmaceutical Group Co. Ltd. Chengdu ChinaDepartment of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy Fudan University Shanghai ChinaAbstract Ciprofol (HSK3486) is a newly developed, highly selective γ‐aminobutyric acid‐A (GABAA) receptor potentiator that is recently approved for a new indication of sedation for patients in the intensive care unit (ICU) in China. This analysis aimed to characterize the population pharmacokinetics (PopPKs) of ciprofol and evaluate the relationship of exposure with hypotension in mechanically ventilated patients in the ICU. A total of 462 subjects with 3918 concentration measurements from two clinical trials of mechanically ventilated patients in the ICU, four clinical trials of elective surgical patients, and six clinical trials of healthy subjects were used in the PopPK analysis. Exposure–safety relationship for hypotension was evaluated based on the data gathered from 112 subjects in two clinical trials of mechanically ventilated patients in the ICU. Ciprofol pharmacokinetics (PKs) was adequately described by a three‐compartment linear disposition model with first‐order elimination. Body weight, age, sex, blood sampling site (vein vs. arterial), study design (long‐term infusion vs. short‐term infusion), and patient population (ICU vs. non‐ICU) were identified as statistically significant covariates on the PKs of ciprofol. Within the exposure range of the mechanically ventilated ICU patient population, no meaningful association was observed between ciprofol exposure and the incidence of hypotension. These results support the dosing regimen currently used in mechanically ventilated patients in the ICU.https://doi.org/10.1002/psp4.13121 |
| spellingShingle | Lu Liu Kun Wang Zhongyi Sun Pangke Yan Mengyue Hu Xiao Liu Meixia Chen Nan Wu Xiaoqiang Xiang Pharmacokinetics and exposure–safety relationship of ciprofol for sedation in mechanically ventilated patients in the intensive care unit CPT: Pharmacometrics & Systems Pharmacology |
| title | Pharmacokinetics and exposure–safety relationship of ciprofol for sedation in mechanically ventilated patients in the intensive care unit |
| title_full | Pharmacokinetics and exposure–safety relationship of ciprofol for sedation in mechanically ventilated patients in the intensive care unit |
| title_fullStr | Pharmacokinetics and exposure–safety relationship of ciprofol for sedation in mechanically ventilated patients in the intensive care unit |
| title_full_unstemmed | Pharmacokinetics and exposure–safety relationship of ciprofol for sedation in mechanically ventilated patients in the intensive care unit |
| title_short | Pharmacokinetics and exposure–safety relationship of ciprofol for sedation in mechanically ventilated patients in the intensive care unit |
| title_sort | pharmacokinetics and exposure safety relationship of ciprofol for sedation in mechanically ventilated patients in the intensive care unit |
| url | https://doi.org/10.1002/psp4.13121 |
| work_keys_str_mv | AT luliu pharmacokineticsandexposuresafetyrelationshipofciprofolforsedationinmechanicallyventilatedpatientsintheintensivecareunit AT kunwang pharmacokineticsandexposuresafetyrelationshipofciprofolforsedationinmechanicallyventilatedpatientsintheintensivecareunit AT zhongyisun pharmacokineticsandexposuresafetyrelationshipofciprofolforsedationinmechanicallyventilatedpatientsintheintensivecareunit AT pangkeyan pharmacokineticsandexposuresafetyrelationshipofciprofolforsedationinmechanicallyventilatedpatientsintheintensivecareunit AT mengyuehu pharmacokineticsandexposuresafetyrelationshipofciprofolforsedationinmechanicallyventilatedpatientsintheintensivecareunit AT xiaoliu pharmacokineticsandexposuresafetyrelationshipofciprofolforsedationinmechanicallyventilatedpatientsintheintensivecareunit AT meixiachen pharmacokineticsandexposuresafetyrelationshipofciprofolforsedationinmechanicallyventilatedpatientsintheintensivecareunit AT nanwu pharmacokineticsandexposuresafetyrelationshipofciprofolforsedationinmechanicallyventilatedpatientsintheintensivecareunit AT xiaoqiangxiang pharmacokineticsandexposuresafetyrelationshipofciprofolforsedationinmechanicallyventilatedpatientsintheintensivecareunit |