Pharmacokinetics of Haloperidol in Critically Ill Patients: Is There an Association with Inflammation?

Li, Letao; Sassen, Sebastiaan D. T.; Jagt, Mathieu van der; Endeman, Henrik; Koch, Birgit C. P.; Hunfeld, Nicole

doi:10.3390/pharmaceutics14030549

Cited by 3 publications

(1 citation statement)

References 41 publications

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“…The impact of C-reactive protein (CRP) on exposure to haloperidol following the administration of low haloperidol doses in critically ill adults was described in contribution (16). By constructing its parametric Bayesian model and by performing Monte Carlo simulations, the authors showed that the clearance of haloperidol is negatively correlated with increasing CRP up to approximately 50 mg/L, pointing to the utility of individualized dosing at the intensive care unit to overcome delirium.…”

Section: Miscellaneous Drugsmentioning

confidence: 99%

Therapeutic Drug Monitoring and Pharmacokinetics-Based Individualization of Drug Therapy

Karvaly,

Vásárhelyi

2024

Pharmaceutics

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Section: Miscellaneous Drugsmentioning

confidence: 99%

Therapeutic Drug Monitoring and Pharmacokinetics-Based Individualization of Drug Therapy

Karvaly,

Vásárhelyi

2024

Pharmaceutics

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The relation between inflammatory biomarkers and drug pharmacokinetics in the critically ill patients: a scoping review

Li,

Zinger,

Sassen

et al. 2024

Crit Care

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Background The level of inflammation alters drug pharmacokinetics (PK) in critically ill patients. This might compromise treatment efficacy. Understanding the specific effects of inflammation, measured by biomarkers, on drug absorption, distribution, metabolism, and excretion is might help in optimizing dosing strategies. Objectives This review investigates the relationship between inflammatory biomarkers and PK parameters absorption, distribution, metabolism and excretion (ADME) in critically ill patients, providing insight in the complexity of dosing drugs in critically ill patients. Method Following PRISMA guidelines, we conducted a comprehensive search of Medline, Embase, Web of Science, and Cochrane databases (January 1946–November 2023). Studies examining inflammatory biomarkers, PK parameters, or drug exposure in critically ill patients were included. Records were screened by title, abstract, and full text, with any discrepancies resolved through discussion or consultation with a third reviewer. Results Of the 4479 records screened, 31 met our inclusion criteria: 2 on absorption, 7 on distribution, 17 on metabolism, and 6 on excretion. In general, results are only available for a limited number of drugs, and most studies are done only looking at one of the components of ADME. Higher levels of inflammatory biomarkers may increase or decrease drug absorption depending on whether the drug undergoes hepatic first-pass elimination. For drug distribution, inflammation is negatively correlated with drug protein binding capacity, positively correlated with cerebrospinal fluid penetration, and negatively correlated with peritoneal penetration. Metabolizing capacity of most drugs was inversely correlated with inflammatory biomarkers. Regarding excretion, inflammation can lead to reduced drug clearance, except in the neonatal population. Conclusion Inflammatory biomarkers can offer valuable information regarding altered PK in critically ill patients. Our findings emphasize the need to consider inflammation-driven PK variability when individualizing drug therapy in this setting, at the same time research is limited to certain drugs and needs further research, also including pharmacodynamics.

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Development and Evaluation of a Physiologically Based Pharmacokinetic Model for Predicting Haloperidol Exposure in Healthy and Disease Populations

Alasmari

et al. 2022

Pharmaceutics

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The physiologically based pharmacokinetic (PBPK) approach can be used to develop mathematical models for predicting the absorption, distribution, metabolism, and elimination (ADME) of administered drugs in virtual human populations. Haloperidol is a typical antipsychotic drug with a narrow therapeutic index and is commonly used in the management of several medical conditions, including psychotic disorders. Due to the large interindividual variability among patients taking haloperidol, it is very likely for them to experience either toxic or subtherapeutic effects. We intend to develop a haloperidol PBPK model for identifying the potential sources of pharmacokinetic (PK) variability after intravenous and oral administration by using the population-based simulator, PK-Sim. The model was initially developed and evaluated to predict the PK of haloperidol and its reduced metabolite in adult healthy population after intravenous and oral administration. After evaluating the developed PBPK model in healthy adults, it was used to predict haloperidol–rifampicin drug–drug interaction and was extended to tuberculosis patients. The model evaluation was performed using visual assessments, prediction error, and mean fold error of the ratio of the observed-to-predicted values of the PK parameters. The predicted PK values were in good agreement with the corresponding reported values. The effects of the pathophysiological changes and enzyme induction associated with tuberculosis and its treatment, respectively, on haloperidol PK, have been predicted precisely. For all clinical scenarios that were evaluated, the predicted values were within the acceptable two-fold error range.

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Pharmacokinetics of Haloperidol in Critically Ill Patients: Is There an Association with Inflammation?

Cited by 3 publications

References 41 publications

Therapeutic Drug Monitoring and Pharmacokinetics-Based Individualization of Drug Therapy

Therapeutic Drug Monitoring and Pharmacokinetics-Based Individualization of Drug Therapy

The relation between inflammatory biomarkers and drug pharmacokinetics in the critically ill patients: a scoping review

Development and Evaluation of a Physiologically Based Pharmacokinetic Model for Predicting Haloperidol Exposure in Healthy and Disease Populations

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