ABSTRACT
BACKGROUND: Previously, a linked pharmacokinetic-pharmacodynamic model (the Kim model) of propofol with concurrent infusion of remifentanil was developed for children aged 2–12 years. There are few options for pharmacokinetic-pharmacodynamic model of propofol for children under two years old. We performed an external validation of the Kim model for children under two years old to evaluate whether the model is applicable to this age group.METHODS: Twenty-four children were enrolled. After routine anesthetic induction, a continuous infusion of 2% propofol and remifentanil was commenced using the Kim model. The target effect-site concentration of propofol was set as 2, 3, 4, and 5 μg/mL, followed by arterial blood sampling after 10 min of each equilibrium. Population estimates of four parameters—pooled bias, inaccuracy, divergence, and wobble—were used to evaluate the performance of the Kim model.RESULTS: A total of 95 plasma concentrations were used for evaluation of the Kim model. The population estimate (95% confidence interval) of bias was −0.96% (−8.45%, 6.54%) and that of inaccuracy was 21.0% (15.0%–27.0%) for the plasma concentration of propofol.CONCLUSION: The pooled bias and inaccuracy of the pharmacokinetic predictions are clinically acceptable. Therefore, our external validation of the Kim model indicated that the model can be applicable to target-controlled infusion of propofol in children younger than 2 years, with the recommended use of actual bispectral index monitoring in clinical settings that remifentanil is present. Trial Registration Clinical Research Information Service Identifier:TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0001752
ABSTRACT
BACKGROUND@#Previously, a linked pharmacokinetic-pharmacodynamic model (the Kim model) of propofol with concurrent infusion of remifentanil was developed for children aged 2–12 years. There are few options for pharmacokinetic-pharmacodynamic model of propofol for children under two years old. We performed an external validation of the Kim model for children under two years old to evaluate whether the model is applicable to this age group.@*METHODS@#Twenty-four children were enrolled. After routine anesthetic induction, a continuous infusion of 2% propofol and remifentanil was commenced using the Kim model. The target effect-site concentration of propofol was set as 2, 3, 4, and 5 μg/mL, followed by arterial blood sampling after 10 min of each equilibrium. Population estimates of four parameters—pooled bias, inaccuracy, divergence, and wobble—were used to evaluate the performance of the Kim model.@*RESULTS@#A total of 95 plasma concentrations were used for evaluation of the Kim model. The population estimate (95% confidence interval) of bias was −0.96% (−8.45%, 6.54%) and that of inaccuracy was 21.0% (15.0%–27.0%) for the plasma concentration of propofol.@*CONCLUSION@#The pooled bias and inaccuracy of the pharmacokinetic predictions are clinically acceptable. Therefore, our external validation of the Kim model indicated that the model can be applicable to target-controlled infusion of propofol in children younger than 2 years, with the recommended use of actual bispectral index monitoring in clinical settings that remifentanil is present.Trial RegistrationClinical Research Information Service Identifier:TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0001752
ABSTRACT
BACKGROUND@#Previously, a linked pharmacokinetic-pharmacodynamic model (the Kim model) of propofol with concurrent infusion of remifentanil was developed for children aged 2–12 years. There are few options for pharmacokinetic-pharmacodynamic model of propofol for children under two years old. We performed an external validation of the Kim model for children under two years old to evaluate whether the model is applicable to this age group.@*METHODS@#Twenty-four children were enrolled. After routine anesthetic induction, a continuous infusion of 2% propofol and remifentanil was commenced using the Kim model. The target effect-site concentration of propofol was set as 2, 3, 4, and 5 μg/mL, followed by arterial blood sampling after 10 min of each equilibrium. Population estimates of four parameters—pooled bias, inaccuracy, divergence, and wobble—were used to evaluate the performance of the Kim model.@*RESULTS@#A total of 95 plasma concentrations were used for evaluation of the Kim model. The population estimate (95% confidence interval) of bias was −0.96% (−8.45%, 6.54%) and that of inaccuracy was 21.0% (15.0%–27.0%) for the plasma concentration of propofol.@*CONCLUSION@#The pooled bias and inaccuracy of the pharmacokinetic predictions are clinically acceptable. Therefore, our external validation of the Kim model indicated that the model can be applicable to target-controlled infusion of propofol in children younger than 2 years, with the recommended use of actual bispectral index monitoring in clinical settings that remifentanil is present.Trial RegistrationClinical Research Information Service Identifier:TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0001752
ABSTRACT
Tryptophan metabolites regulate a variety of physiological processes, and their downstream metabolites enter the kynurenine pathway. Age-related changes of metabolites and activities of associated enzymes in this pathway are suggestable and would be potential intervention targets. Blood levels of serum tryptophan metabolites in C57BL/6 mice of different ages, ranging from 6 weeks to 10 months, were assessed using high-performance liquid chromatography, and the enzyme activities for each metabolic step were estimated using the ratio of appropriate metabolite levels. Mice were subjected to voluntary chronic aerobic exercise or high-fat diet to assess their ability to rescue age-related alterations in the kynurenine pathway. The ratio of serum kynurenic acid (KYNA) to 3-hydroxylkynurenine (3-HK) decreased with advancing age. Voluntary chronic aerobic exercise and high-fat diet rescued the decreased KYNA/3-HK ratio in the 6-month-old and 8-month-old mice groups. Tryptophan metabolites and their associated enzyme activities were significantly altered during aging, and the KYNA/3-HK ratio was a meaningful indicator of aging. Exercise and high-fat diet could potentially recover the reduction of the KYNA/3-HK ratio in the elderly.