Population pharmacokinetic and pharmacodynamic model of propofol externally validated in Korean elderly subjects
The Eleveld propofol pharmacokinetic (PK) model, which was developed based on a broad range of populations, showed greater bias (− 27%) in elderly subjects in a previous validation study conducted by Vellinga and colleagues. We aimed to develop and externally validate a new PK-pharmacodynamic (PK-PD...
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| Published in | Journal of pharmacokinetics and pharmacodynamics Vol. 50; no. 2; pp. 97 - 109 |
|---|---|
| Main Authors | , , |
| Format | Journal Article |
| Language | English |
| Published |
New York
Springer US
01.04.2023
Springer Nature B.V |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1567-567X 1573-8744 1573-8744 |
| DOI | 10.1007/s10928-022-09836-6 |
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| Abstract | The Eleveld propofol pharmacokinetic (PK) model, which was developed based on a broad range of populations, showed greater bias (− 27%) in elderly subjects in a previous validation study conducted by Vellinga and colleagues. We aimed to develop and externally validate a new PK-pharmacodynamic (PK-PD) model of propofol for elderly subjects. A population PK-PD model was constructed using propofol plasma concentrations and bispectral index (BIS) values that were obtained from 31 subjects aged 65 years older in previously published phase I studies. The predictive performance of the newly-developed PK-PD model (Choi model) was assessed in a separate Korean elderly population and compared with that of the Eleveld model. A three-compartment mammillary model using an allometric expression and a sigmoid E
max
model well-described the time courses of propofol concentrations and BIS values. The
V
1
,
V
2
,
V
3
,
Cl
,
Q
1
,
Q
2
,
E
0
,
E
max
,
Ce
50
,
γ
, and
k
e0
of a 60-kg subject were 8.36, 58.0, 650 L, 1.26, 0.917, 0.669 L/min, 92.1, 18.7, 2.21 μg/mL, 2.89, and 0.138 /min, respectively. In the Choi model and Eleveld model, pooled biases (95% CI) of the propofol concentration were 7.78 ( 3.09–12.49) and 16.70 (9.46–23.93) and pooled inaccuracies were 22.84 (18.87–26.81) and 24.85 (18.07–31.63), respectively. The Choi PK model was less biased than the Eleveld PK model in Korean elderly subjects (age range: 65.0–79.0 yr; weight range: 45.0–75.3 kg). Our results suggest that the Choi PK model, particularly, is applicable to target-controlled infusion in non-obese Korean elderly subjects. |
|---|---|
| AbstractList | The Eleveld propofol pharmacokinetic (PK) model, which was developed based on a broad range of populations, showed greater bias (- 27%) in elderly subjects in a previous validation study conducted by Vellinga and colleagues. We aimed to develop and externally validate a new PK-pharmacodynamic (PK-PD) model of propofol for elderly subjects. A population PK-PD model was constructed using propofol plasma concentrations and bispectral index (BIS) values that were obtained from 31 subjects aged 65 years older in previously published phase I studies. The predictive performance of the newly-developed PK-PD model (Choi model) was assessed in a separate Korean elderly population and compared with that of the Eleveld model. A three-compartment mammillary model using an allometric expression and a sigmoid E
model well-described the time courses of propofol concentrations and BIS values. The V
, V
, V
, Cl, Q
, Q
, E
, E
, Ce
, γ, and k
of a 60-kg subject were 8.36, 58.0, 650 L, 1.26, 0.917, 0.669 L/min, 92.1, 18.7, 2.21 μg/mL, 2.89, and 0.138 /min, respectively. In the Choi model and Eleveld model, pooled biases (95% CI) of the propofol concentration were 7.78 ( 3.09-12.49) and 16.70 (9.46-23.93) and pooled inaccuracies were 22.84 (18.87-26.81) and 24.85 (18.07-31.63), respectively. The Choi PK model was less biased than the Eleveld PK model in Korean elderly subjects (age range: 65.0-79.0 yr; weight range: 45.0-75.3 kg). Our results suggest that the Choi PK model, particularly, is applicable to target-controlled infusion in non-obese Korean elderly subjects. The Eleveld propofol pharmacokinetic (PK) model, which was developed based on a broad range of populations, showed greater bias (- 27%) in elderly subjects in a previous validation study conducted by Vellinga and colleagues. We aimed to develop and externally validate a new PK-pharmacodynamic (PK-PD) model of propofol for elderly subjects. A population PK-PD model was constructed using propofol plasma concentrations and bispectral index (BIS) values that were obtained from 31 subjects aged 65 years older in previously published phase I studies. The predictive performance of the newly-developed PK-PD model (Choi model) was assessed in a separate Korean elderly population and compared with that of the Eleveld model. A three-compartment mammillary model using an allometric expression and a sigmoid Emax model well-described the time courses of propofol concentrations and BIS values. The V1, V2, V3, Cl, Q1, Q2, E0, Emax, Ce50, γ, and ke0 of a 60-kg subject were 8.36, 58.0, 650 L, 1.26, 0.917, 0.669 L/min, 92.1, 18.7, 2.21 μg/mL, 2.89, and 0.138 /min, respectively. In the Choi model and Eleveld model, pooled biases (95% CI) of the propofol concentration were 7.78 ( 3.09-12.49) and 16.70 (9.46-23.93) and pooled inaccuracies were 22.84 (18.87-26.81) and 24.85 (18.07-31.63), respectively. The Choi PK model was less biased than the Eleveld PK model in Korean elderly subjects (age range: 65.0-79.0 yr; weight range: 45.0-75.3 kg). Our results suggest that the Choi PK model, particularly, is applicable to target-controlled infusion in non-obese Korean elderly subjects.The Eleveld propofol pharmacokinetic (PK) model, which was developed based on a broad range of populations, showed greater bias (- 27%) in elderly subjects in a previous validation study conducted by Vellinga and colleagues. We aimed to develop and externally validate a new PK-pharmacodynamic (PK-PD) model of propofol for elderly subjects. A population PK-PD model was constructed using propofol plasma concentrations and bispectral index (BIS) values that were obtained from 31 subjects aged 65 years older in previously published phase I studies. The predictive performance of the newly-developed PK-PD model (Choi model) was assessed in a separate Korean elderly population and compared with that of the Eleveld model. A three-compartment mammillary model using an allometric expression and a sigmoid Emax model well-described the time courses of propofol concentrations and BIS values. The V1, V2, V3, Cl, Q1, Q2, E0, Emax, Ce50, γ, and ke0 of a 60-kg subject were 8.36, 58.0, 650 L, 1.26, 0.917, 0.669 L/min, 92.1, 18.7, 2.21 μg/mL, 2.89, and 0.138 /min, respectively. In the Choi model and Eleveld model, pooled biases (95% CI) of the propofol concentration were 7.78 ( 3.09-12.49) and 16.70 (9.46-23.93) and pooled inaccuracies were 22.84 (18.87-26.81) and 24.85 (18.07-31.63), respectively. The Choi PK model was less biased than the Eleveld PK model in Korean elderly subjects (age range: 65.0-79.0 yr; weight range: 45.0-75.3 kg). Our results suggest that the Choi PK model, particularly, is applicable to target-controlled infusion in non-obese Korean elderly subjects. The Eleveld propofol pharmacokinetic (PK) model, which was developed based on a broad range of populations, showed greater bias (− 27%) in elderly subjects in a previous validation study conducted by Vellinga and colleagues. We aimed to develop and externally validate a new PK-pharmacodynamic (PK-PD) model of propofol for elderly subjects. A population PK-PD model was constructed using propofol plasma concentrations and bispectral index (BIS) values that were obtained from 31 subjects aged 65 years older in previously published phase I studies. The predictive performance of the newly-developed PK-PD model (Choi model) was assessed in a separate Korean elderly population and compared with that of the Eleveld model. A three-compartment mammillary model using an allometric expression and a sigmoid Emax model well-described the time courses of propofol concentrations and BIS values. The V1, V2, V3, Cl, Q1, Q2, E0, Emax, Ce50, γ, and ke0 of a 60-kg subject were 8.36, 58.0, 650 L, 1.26, 0.917, 0.669 L/min, 92.1, 18.7, 2.21 μg/mL, 2.89, and 0.138 /min, respectively. In the Choi model and Eleveld model, pooled biases (95% CI) of the propofol concentration were 7.78 ( 3.09–12.49) and 16.70 (9.46–23.93) and pooled inaccuracies were 22.84 (18.87–26.81) and 24.85 (18.07–31.63), respectively. The Choi PK model was less biased than the Eleveld PK model in Korean elderly subjects (age range: 65.0–79.0 yr; weight range: 45.0–75.3 kg). Our results suggest that the Choi PK model, particularly, is applicable to target-controlled infusion in non-obese Korean elderly subjects. The Eleveld propofol pharmacokinetic (PK) model, which was developed based on a broad range of populations, showed greater bias (− 27%) in elderly subjects in a previous validation study conducted by Vellinga and colleagues. We aimed to develop and externally validate a new PK-pharmacodynamic (PK-PD) model of propofol for elderly subjects. A population PK-PD model was constructed using propofol plasma concentrations and bispectral index (BIS) values that were obtained from 31 subjects aged 65 years older in previously published phase I studies. The predictive performance of the newly-developed PK-PD model (Choi model) was assessed in a separate Korean elderly population and compared with that of the Eleveld model. A three-compartment mammillary model using an allometric expression and a sigmoid E max model well-described the time courses of propofol concentrations and BIS values. The V 1 , V 2 , V 3 , Cl , Q 1 , Q 2 , E 0 , E max , Ce 50 , γ , and k e0 of a 60-kg subject were 8.36, 58.0, 650 L, 1.26, 0.917, 0.669 L/min, 92.1, 18.7, 2.21 μg/mL, 2.89, and 0.138 /min, respectively. In the Choi model and Eleveld model, pooled biases (95% CI) of the propofol concentration were 7.78 ( 3.09–12.49) and 16.70 (9.46–23.93) and pooled inaccuracies were 22.84 (18.87–26.81) and 24.85 (18.07–31.63), respectively. The Choi PK model was less biased than the Eleveld PK model in Korean elderly subjects (age range: 65.0–79.0 yr; weight range: 45.0–75.3 kg). Our results suggest that the Choi PK model, particularly, is applicable to target-controlled infusion in non-obese Korean elderly subjects. |
| Author | Kim, Kyung Mi Noh, Gyu-Jeong Choi, Byung-Moon |
| Author_xml | – sequence: 1 givenname: Kyung Mi orcidid: 0000-0001-6893-1539 surname: Kim fullname: Kim, Kyung Mi organization: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine – sequence: 2 givenname: Byung-Moon orcidid: 0000-0002-6561-8851 surname: Choi fullname: Choi, Byung-Moon email: byungmoonchoi7@gmail.com organization: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine – sequence: 3 givenname: Gyu-Jeong orcidid: 0000-0002-1964-9294 surname: Noh fullname: Noh, Gyu-Jeong organization: Departments of Anesthesiology and Pain Medicine, Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/36522561$$D View this record in MEDLINE/PubMed |
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| Keywords | Model Pharmacodynamics Aged Propofol Pharmacokinetics Performance |
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| Snippet | The Eleveld propofol pharmacokinetic (PK) model, which was developed based on a broad range of populations, showed greater bias (− 27%) in elderly subjects in... The Eleveld propofol pharmacokinetic (PK) model, which was developed based on a broad range of populations, showed greater bias (- 27%) in elderly subjects in... |
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| SubjectTerms | Aged Anesthetics, Intravenous - pharmacokinetics Biochemistry Biomedical and Life Sciences Biomedical Engineering and Bioengineering Biomedicine Humans Models, Biological Original Paper Pharmacodynamics Pharmacokinetics Pharmacology/Toxicology Pharmacy Propofol Propofol - pharmacokinetics Republic of Korea Veterinary Medicine/Veterinary Science |
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| Title | Population pharmacokinetic and pharmacodynamic model of propofol externally validated in Korean elderly subjects |
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