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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    This result may indicate a differential effect from that for the mathematic calculation, and the temperature effect on CYP2C activity needs further investigation.

    These simulated curves were compared with the observed data.

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    We hypothesized that the metabolism of P probe substrates decreases during cooling because of the acute effect of hypothermia on the enzyme activity and that these alterations would be isoform-specific. Kirwan et al.

    images caldwell 1982 ac 341 hlb

    Time course of plasma concentrations obtained for midazolam, diclofenac, dextromethorphan, and chlorzoxazone from 0 to 8 h after intravenous bolus of 0.

    Caldwell ); only a high quality, competent team can identify the . DW has improved the consistency of data to users (or *** applications). The Bibliography forlike its predecessor forhas been organized of Representative British and American Actors and Ac- Stadler, Ernst.

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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.

    Kirwan et al.

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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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    hpophile-balance (HLB) of the emulsifier and the freezing process. Degree Surface ac¬ tive molecules . Higher freezing rates have been shown by Caldwell et al.

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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.

    images caldwell 1982 ac 341 hlb

    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.

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    1. Open in a separate window. Many of the drugs used in CA patients do not have readily measurable pharmacodynamic endpoints and have narrow therapeutic indices.

    2. The first-order conditional estimation method with interaction was used to estimate all parameters. A decrease in the OFV of 3.