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.
Tuberculosis remains a major infectious cause of morbidity and mortality worldwide. Current antibiotic regimens, constructed prior to the development of modern pharmacokinetic-pharmacodynamic (PK-PD) tools, are based on incomplete understanding of exposure-response relationships in drug susceptible and multidrug resistant tuberculosis. Preclinical and population PK data suggest that clinical PK-PD studies may enable therapeutic drug monitoring for some agents and revised dosing for others. Future clinical PK-PD challenges include: incorporation of PK methods to assay free concentrations for all active metabolites; selection of appropriate early outcome measures which reflect therapeutic response; elucidation of genetic contributors to interindividual PK variability; conduct of targeted studies on special populations (including children); and measurement of PK-PD parameters at the site of disease.
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