At 1 h after resuscitation, the glucose level in the CA hypothermia group was the lowest among groups. There was no significant difference found in clearances of dextromethorphan among four groups. Individual generated clearances versus temperature from final pharmacokinetic models for midazolam Adiclofenac Band chlorzoxazone C. External link. Support Center Support Center. At present, no studies have been conducted to explore the exact mechanisms of these alterations; however, the reduction in volume of distribution has been consistent across studies and warrants future mechanistic evaluation.
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The peripheral compartment volume of chlorzoxazone in hypothermia was estimated to be The solid line in the plot is the line of unity.
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The blood sample volume was replaced with an equal volume of normal saline. Because our drug compounds were not administered until 90 min after resuscitation, it is highly unlikely that hepatic blood flow changes at this later time point would have a significant effect on the hepatic clearance of low hepatic extraction probe drugs. Doses of bicarbonate were given as needed to correct acidosis. Time-concentration curves from the four groups for midazolam, diclofenac, dextromethorphan, and chlorzoxazone are shown in Fig.
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External link. In addition, during hypothermia after CA, the alterations in normal drug metabolism can be quite complex because of suppressed effects from heart failure, multiple organ dysfunction, and temperature.
Noncompartmental analyses for pharmacokinetic variables of each probe drug from different treatments were compared by one-way ANOVA with Bonferroni post hoc testing. The individual clearances generated for each time point from each of the four groups were visualized as a graph for further evaluation. Hypothermia was induced starting 60 min after resuscitation.
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|All animals were acclimated for 1 week before the experiment.
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Poloyac, Salk Hall, Terrace St. Physiological variables were compared by repeated-measures ANOVA among groups and across time with Bonferroni post hoc testing. However, in the population PK model, after we grouped hypothermia groups versus normothermia groups, there was a weak association between hypothermia and reduced clearance of diclofenac. Xcalibur 2. The concentration of midazolam at 4 h after administration was significantly greater in critically ill patients compared with that in normal subjects.
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Despite the benefit of therapeutic hypothermia, whole-body cooling after resuscitation complicates drug therapy because of its potential effects on both drug disposition and response. Parameter estimates and S.
The concentration of midazolam at 4 h after administration was significantly greater in critically ill patients compared with that in normal subjects. The solid line in the plot is the line of unity. Probe drug plasma concentrations were measured simultaneously by UPLC-triple quadrupole mass spectrometry.
Normal saline solution 1. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.
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|The clearances of midazolam in sham hypothermia, CA normothermia, and CA hypothermia groups were Further refinement of the error model was performed as needed.
The specific ion transition for midazolam, diclofenac, dextromethorphan, and chlorzoxazone were Population pharmacokinetic parameter estimates from a nonlinear mixed-effect model for midazolam, diclofenac, dextromethorphan, and chlorzoxazone.
There was a hypothermia-CA interaction effect on the clearance of chlorzoxazone.