Inter-individual variability in propofol pharmacokinetic/pharmacodynamic (PK/PD) model – a sensitivity analysis
Inter-individual variability is a major challenge to guarantee adequate anaesthesia in patients across the population. This variability can occur as a result of patient physiology (e.g. age and weight), variations in the pharmacokinetic (PK) process and differences in the pharmacodynamic (PD) functi...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Scholars Academic and Scientific Publisher
2016
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| Online Access: | http://psasir.upm.edu.my/id/eprint/54599/ http://psasir.upm.edu.my/id/eprint/54599/1/Inter-individual%20variability%20in%20propofol%20pharmacokinetic%2C%20pharmacodynamic%20PK%2C%20PD%20model%20%E2%80%93%20a%20sensitivity%20analysis.pdf |
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| author | Chang, J. J. Syafiie, S. Raja Ahmad, Raja Mohd Kamil Lim, T. A. |
| author_facet | Chang, J. J. Syafiie, S. Raja Ahmad, Raja Mohd Kamil Lim, T. A. |
| author_sort | Chang, J. J. |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | Inter-individual variability is a major challenge to guarantee adequate anaesthesia in patients across the population. This variability can occur as a result of patient physiology (e.g. age and weight), variations in the pharmacokinetic (PK) process and differences in the pharmacodynamic (PD) function. For a safe and effective drug administration, it is important to recognise which and when these factors of variability cause a higher uncertainty on depth of anaesthesia. This study aimed to quantify the influence of these input factors on the uncertainty in Bispectral Index (BIS). In this study, Sobol’ variance-based sensitivity analysis was performed on Schnider PK/PD model. Nine factors were evaluated: age, body weight, height, V1, V3, Cl1, Cl3, Ce50, and γ. The importance of these factors were ranked according to their total sensitivity indices. It was found that Ce50 has the most determining role on BIS prediction. γ is a significant factor during the induction phase. The PD model alone was found to responsible for 70% to 90% of BIS uncertainty during the maintenance phase. The variability of height has negligible influence on BIS prediction and can be omitted from the PK/PD model. |
| first_indexed | 2025-11-15T10:40:29Z |
| format | Article |
| id | upm-54599 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T10:40:29Z |
| publishDate | 2016 |
| publisher | Scholars Academic and Scientific Publisher |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-545992022-05-25T08:22:14Z http://psasir.upm.edu.my/id/eprint/54599/ Inter-individual variability in propofol pharmacokinetic/pharmacodynamic (PK/PD) model – a sensitivity analysis Chang, J. J. Syafiie, S. Raja Ahmad, Raja Mohd Kamil Lim, T. A. Inter-individual variability is a major challenge to guarantee adequate anaesthesia in patients across the population. This variability can occur as a result of patient physiology (e.g. age and weight), variations in the pharmacokinetic (PK) process and differences in the pharmacodynamic (PD) function. For a safe and effective drug administration, it is important to recognise which and when these factors of variability cause a higher uncertainty on depth of anaesthesia. This study aimed to quantify the influence of these input factors on the uncertainty in Bispectral Index (BIS). In this study, Sobol’ variance-based sensitivity analysis was performed on Schnider PK/PD model. Nine factors were evaluated: age, body weight, height, V1, V3, Cl1, Cl3, Ce50, and γ. The importance of these factors were ranked according to their total sensitivity indices. It was found that Ce50 has the most determining role on BIS prediction. γ is a significant factor during the induction phase. The PD model alone was found to responsible for 70% to 90% of BIS uncertainty during the maintenance phase. The variability of height has negligible influence on BIS prediction and can be omitted from the PK/PD model. Scholars Academic and Scientific Publisher 2016 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/54599/1/Inter-individual%20variability%20in%20propofol%20pharmacokinetic%2C%20pharmacodynamic%20PK%2C%20PD%20model%20%E2%80%93%20a%20sensitivity%20analysis.pdf Chang, J. J. and Syafiie, S. and Raja Ahmad, Raja Mohd Kamil and Lim, T. A. (2016) Inter-individual variability in propofol pharmacokinetic/pharmacodynamic (PK/PD) model – a sensitivity analysis. Scholars Journal of Applied Medical Science, 4 (11B). 3936 - 3942. ISSN 2347-954X; ESSN: 2320-6691 http://saspublisher.com/sjams-411/ 10.21276/sjams.2016.4.11.16 |
| spellingShingle | Chang, J. J. Syafiie, S. Raja Ahmad, Raja Mohd Kamil Lim, T. A. Inter-individual variability in propofol pharmacokinetic/pharmacodynamic (PK/PD) model – a sensitivity analysis |
| title | Inter-individual variability in propofol pharmacokinetic/pharmacodynamic (PK/PD) model – a sensitivity analysis |
| title_full | Inter-individual variability in propofol pharmacokinetic/pharmacodynamic (PK/PD) model – a sensitivity analysis |
| title_fullStr | Inter-individual variability in propofol pharmacokinetic/pharmacodynamic (PK/PD) model – a sensitivity analysis |
| title_full_unstemmed | Inter-individual variability in propofol pharmacokinetic/pharmacodynamic (PK/PD) model – a sensitivity analysis |
| title_short | Inter-individual variability in propofol pharmacokinetic/pharmacodynamic (PK/PD) model – a sensitivity analysis |
| title_sort | inter-individual variability in propofol pharmacokinetic/pharmacodynamic (pk/pd) model – a sensitivity analysis |
| url | http://psasir.upm.edu.my/id/eprint/54599/ http://psasir.upm.edu.my/id/eprint/54599/ http://psasir.upm.edu.my/id/eprint/54599/ http://psasir.upm.edu.my/id/eprint/54599/1/Inter-individual%20variability%20in%20propofol%20pharmacokinetic%2C%20pharmacodynamic%20PK%2C%20PD%20model%20%E2%80%93%20a%20sensitivity%20analysis.pdf |