Browsing by Subject "ketamine"

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    ItemOpen Access
    Association between simulated ketamine exposures and oxygen saturations in children.
    (International journal of pharmacokinetics, 2023-02) Commander, Sarah Jane; Gonzalez, Daniel; Kumar, Karan R; Spears, Tracy; Cohen-Wolkowiez, Michael; Zimmerman, Kanecia O; Lee, Jan Hau; Hornik, Christoph P

    Aim

    We performed a real-world data analysis to evaluate the relationship between simulated ketamine exposures and oxygen desaturation in children.

    Materials & methods

    A previously developed population pharmacokinetic model was used to simulate exposures and evaluate target attainment, as well as the association with oxygen desaturation in children ≤17 years treated with intravenous ketamine.

    Results

    In 2022 children, there was no significant association between simulated plasma ketamine concentrations and oxygen saturation; however, a higher cumulative area under the curve was associated with increased odds of progression to significant desaturation (<85%), though magnitude of effect was small.

    Conclusion

    By leveraging a population pharmacokinetic model and real-world data, we confirmed there is no relationship between simulated ketamine plasma concentration and oxygen desaturation.
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    ItemOpen Access
    Serotonin is a Common Thread Linking Different Classes of Antidepressants.
    (Res Sq, 2023-03-28) Witt, Colby E; Mena, Sergio; Holmes, Jordan; Hersey, Melinda; Buchanan, Anna Marie; Parke, Brenna; Saylor, Rachel; Honan, Lauren E; Berger, Shane N; Lumbreras, Sara; Nijhout, Frederik H; Reed, Michael C; Best, Janet; Fadel, James; Schloss, Patrick; Lau, Thorsten; Hashemi, Parastoo
    Depression pathology remains elusive. The monoamine hypothesis has placed much focus on serotonin, but due to the variable clinical efficacy of monoamine reuptake inhibitors, the community is looking for alternative therapies such as ketamine (synaptic plasticity and neurogenesis theory of antidepressant action). There is evidence that different classes of antidepressants may affect serotonin levels; a notion we test here. We measure hippocampal serotonin in mice with voltammetry and study the effects of acute challenges of antidepressants. We find that pseudo-equivalent doses of these drugs similarly raise ambient serotonin levels, despite their differing pharmacodynamics because of differences in Uptake 1 and 2, rapid SERT trafficking and modulation of serotonin by histamine. These antidepressants have different pharmacodynamics but have strikingly similar effects on extracellular serotonin. Our findings suggest that serotonin is a common thread that links clinically effective antidepressants, synergizing different theories of depression (synaptic plasticity, neurogenesis and the monoamine hypothesis).