Articles: biological-models.
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Journal of anesthesia · Dec 2022
Equilibration rate constant, ke0, to determine effect-site concentration for the Masui remimazolam population pharmacokinetic model in general anesthesia patients.
Effect-site concentration is widely used to determine drug dosage in anesthesia practice. To obtain effect-site concentration, a pharmacokinetic model with a corresponding equilibration rate constant between plasma and effect-site, ke0, is necessary. Remimazolam, a novel short-acting benzodiazepine, has been approved as anesthetic/sedative. ⋯ The ke0 value can be calculated using numerical analysis but not algebraic solution. We provide the detail method of the numerical analysis and a tool to have ke0 value easily for the Masui remimazolam PK model. Additionally, we provide a multiple regression model to have ke0 value for the PK model.
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Oxidation-reduction (redox) reactions, and the redox potential (RP) that must be maintained for proper cell function, lie at the heart of physiologic processes in critical illness. Imbalance in RP reflects systemic oxidative stress, and whole blood RP measures have been shown to correlate with oxygen debt level over time in swine traumatic shock. We hypothesize that RP measures reflect changing concentrations of metabolites involved in oxidative stress. To test this hypothesis, we compared blood and urine RP with concentrations of multiple metabolites in a swine traumatic shock model to identify meaningful RP-metabolite relationships. ⋯ Real-time RP measures demonstrate significant relationships with metabolites attributable to metabolic pathways involved in systemic responses to oxidative stress, as well as those involved in these processes. These data support RP measures as a feasible, biologically relevant marker of oxidative stress. As a direct measure of redox state, RP may be a useful biomarker and clinical tool in guiding diagnosis and therapy in states of increased oxidative stress and may offer value as a marker for organ injury in these states as well.
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Sepsis-associated acute kidney injury (SA-AKI) is a frequent complication of sepsis, yet the pathophysiologic mechanisms of SA-AKI are incompletely understood. PERSEVERE is a clinically validated serum biomarker panel with high sensitivity in predicting mortality from sepsis, and recent evidence suggests it can also predict severe, persistent SA-AKI at day 3 of hospitalization among septic children. We developed a murine model of PERSEVERE (mPERSEVERE) to further interrogate the sepsis-related biological underpinnings of SA-AKI using candidate biomarkers within mPERSEVERE. ⋯ The combination of plasma CCL3+KC can predict SA-AKI development in mice at 24-hours following CLP Of these two biomarkers, only renal expression of KC is increased in mice with SA-AKI. Further studies are required to determine if KC directly contributes to the underlying pathobiology of SA-AKI.
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Numerous pharmacokinetic models have been published aiming at more accurate and safer dosing of dexmedetomidine. The vast majority of the developed models underpredict the measured plasma concentrations with respect to the target concentration, especially at plasma concentrations higher than those used in the original studies. The aim of this article was to develop a dexmedetomidine pharmacokinetic model in healthy adults emphasizing linear versus nonlinear kinetics. ⋯ This study developed a nonlinear three-compartment pharmacokinetic model that accurately described dexmedetomidine plasma concentrations. Dexmedetomidine may be safely administered up to target-controlled infusion targets under 2 ng · ml-1 using the Hannivoort model, which assumed linear pharmacokinetics. Consideration should be taken during long-term administration and during an initial loading dose when following the dosing strategies of the current guidelines.