Developing a PK-PD model for propofol in exhaled air and the BIS following fospropofol disodium in beagles
Abstract Background Fospropofol, a water-soluble prodrug of propofol, is metabolized into propofol by alkaline phosphatase after administration. This study aimed to develop a pharmacokinetic-pharmacodynamic (PK-PD) model that correlates the propofol concentration in exhaled air (Ce-pro-f) with its a...
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BMC
2025-02-01
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| Series: | BMC Veterinary Research |
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| Online Access: | https://doi.org/10.1186/s12917-025-04570-w |
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| author | Xiaoxiao Li Pan Chang Xing Liu Yi Kang Zhongjun Zhao Yixiang Duan Wensheng Zhang |
| author_facet | Xiaoxiao Li Pan Chang Xing Liu Yi Kang Zhongjun Zhao Yixiang Duan Wensheng Zhang |
| author_sort | Xiaoxiao Li |
| collection | DOAJ |
| description | Abstract Background Fospropofol, a water-soluble prodrug of propofol, is metabolized into propofol by alkaline phosphatase after administration. This study aimed to develop a pharmacokinetic-pharmacodynamic (PK-PD) model that correlates the propofol concentration in exhaled air (Ce-pro-f) with its anesthetic effects, as measured by the bispectral index (BIS) in beagles. Methods Beagles receiving a single intravenous infusion of fospropofol at varying doses were divided into three groups (n = 6): the DBL-fospro group (15 mg/kg), the DBM-fospro group (30 mg/kg), and the DBH-fospro group (60 mg/kg). Propofol levels were monitored using VUV-TOF MS from pre-administration to recovery. Correlations between Ce-pro-f and blood concentration (Cblood-pro), as well as between Ce-pro-f and the BIS were investigated. PK, PD, and PK-PD models describing the relationship between Ce and BIS were also analyzed. Results Propofol concentration in exhaled air can be quantified using VUV-TOF MS at a mass-to-charge ratio of 177.6. After fospropofol injection, the peak Ce-pro-f was delayed compared to Cblood-pro. The PK model of Ce-pro-f can be described using a noncompartmental approach, corresponding to the linear PK characteristics. Additionally, Ce-pro-f showed a moderate to strong negative correlation with BIS values. In the PK-PD model, the PK component was well characterized by a two-compartment model incorporating a first-order delay to account for the time lag of Ce-pro-f relative to Cblood-pro. The PD component was well fitted by the inhibitory sigmoid Emax model, with an indirect connection model selected to explain the observed lag between BIS signals and Ce-pro-f peaks. Conclusions This study is the first to develop a PK-PD model for exhaled propofol in beagles after fospropofol disodium administration. The PK profile was described by a two-compartment model with a first-order delay, and the PD profile was modeled using an inhibitory sigmoid Emax model with an indirect connection model to capture the lag between BIS and exhaled propofol peaks. |
| format | Article |
| id | doaj-art-1e5d1361020645a2aea1c434432e2a29 |
| institution | OA Journals |
| issn | 1746-6148 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
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| series | BMC Veterinary Research |
| spelling | doaj-art-1e5d1361020645a2aea1c434432e2a292025-08-20T02:16:40ZengBMCBMC Veterinary Research1746-61482025-02-0121111010.1186/s12917-025-04570-wDeveloping a PK-PD model for propofol in exhaled air and the BIS following fospropofol disodium in beaglesXiaoxiao Li0Pan Chang1Xing Liu2Yi Kang3Zhongjun Zhao4Yixiang Duan5Wensheng Zhang6Department of Anesthesiology, West China Hospital, Sichuan UniversityDepartment of Anesthesiology, West China Hospital, Sichuan UniversityDepartment of Anesthesiology, West China Hospital, Sichuan UniversityDepartment of Anesthesiology, West China Hospital, Sichuan UniversitySchool of Mechanical Engineering, Sichuan UniversitySchool of Mechanical Engineering, Sichuan UniversityDepartment of Anesthesiology, West China Hospital, Sichuan UniversityAbstract Background Fospropofol, a water-soluble prodrug of propofol, is metabolized into propofol by alkaline phosphatase after administration. This study aimed to develop a pharmacokinetic-pharmacodynamic (PK-PD) model that correlates the propofol concentration in exhaled air (Ce-pro-f) with its anesthetic effects, as measured by the bispectral index (BIS) in beagles. Methods Beagles receiving a single intravenous infusion of fospropofol at varying doses were divided into three groups (n = 6): the DBL-fospro group (15 mg/kg), the DBM-fospro group (30 mg/kg), and the DBH-fospro group (60 mg/kg). Propofol levels were monitored using VUV-TOF MS from pre-administration to recovery. Correlations between Ce-pro-f and blood concentration (Cblood-pro), as well as between Ce-pro-f and the BIS were investigated. PK, PD, and PK-PD models describing the relationship between Ce and BIS were also analyzed. Results Propofol concentration in exhaled air can be quantified using VUV-TOF MS at a mass-to-charge ratio of 177.6. After fospropofol injection, the peak Ce-pro-f was delayed compared to Cblood-pro. The PK model of Ce-pro-f can be described using a noncompartmental approach, corresponding to the linear PK characteristics. Additionally, Ce-pro-f showed a moderate to strong negative correlation with BIS values. In the PK-PD model, the PK component was well characterized by a two-compartment model incorporating a first-order delay to account for the time lag of Ce-pro-f relative to Cblood-pro. The PD component was well fitted by the inhibitory sigmoid Emax model, with an indirect connection model selected to explain the observed lag between BIS signals and Ce-pro-f peaks. Conclusions This study is the first to develop a PK-PD model for exhaled propofol in beagles after fospropofol disodium administration. The PK profile was described by a two-compartment model with a first-order delay, and the PD profile was modeled using an inhibitory sigmoid Emax model with an indirect connection model to capture the lag between BIS and exhaled propofol peaks.https://doi.org/10.1186/s12917-025-04570-wExhaled airPropofolFospropofolVUV-TOF MSPK-PD model |
| spellingShingle | Xiaoxiao Li Pan Chang Xing Liu Yi Kang Zhongjun Zhao Yixiang Duan Wensheng Zhang Developing a PK-PD model for propofol in exhaled air and the BIS following fospropofol disodium in beagles BMC Veterinary Research Exhaled air Propofol Fospropofol VUV-TOF MS PK-PD model |
| title | Developing a PK-PD model for propofol in exhaled air and the BIS following fospropofol disodium in beagles |
| title_full | Developing a PK-PD model for propofol in exhaled air and the BIS following fospropofol disodium in beagles |
| title_fullStr | Developing a PK-PD model for propofol in exhaled air and the BIS following fospropofol disodium in beagles |
| title_full_unstemmed | Developing a PK-PD model for propofol in exhaled air and the BIS following fospropofol disodium in beagles |
| title_short | Developing a PK-PD model for propofol in exhaled air and the BIS following fospropofol disodium in beagles |
| title_sort | developing a pk pd model for propofol in exhaled air and the bis following fospropofol disodium in beagles |
| topic | Exhaled air Propofol Fospropofol VUV-TOF MS PK-PD model |
| url | https://doi.org/10.1186/s12917-025-04570-w |
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