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Clinical Pharmacokinetics

, Volume 46, Issue 11, pp 897–939 | Cite as

Pharmacokinetic Considerations in Clinical Toxicology

Clinical Applications
Review Article

Abstract

Pharmacokinetic and pharmacodynamic principles should be regarded in the assessment and proper management of patients exposed to a poison. Clinicians must apply these principles to make rational clinical decisions regarding the significance of the poisoning (risk assessment) and to formulate an appropriate management plan. However, pharmacokinetic processes and parameters may be changed in the patient with acute poisoning. This may result from saturation of the capacity of a number of physiological processes due to the high dose, or the toxic effects of the poison may change these processes directly. For example, absorption kinetics may be altered because of increased gastrointestinal transit time (e.g. cholinergic receptor antagonists) or saturable absorption (e.g. methotrexate). Saturation of protein binding may increase the volume of distribution and thereby increase the elimination half-life (e.g. salicylates). Alteration of the acid-base balance (poison-induced or iatrogenic) may also increase or decrease the distribution of a poison. Saturation of metabolism at high doses can prolong toxicity (e.g. phenytoin) or lead to other routes of metabolism that lead to increased toxicity (e.g. paracetamol [acetaminophen]). Excretion may be reduced by saturation of active transporters or decreased renal blood flow.

A better understanding of pharmacokinetic principles should improve the clinical care of patients. It should lead to more accurate interpretation of blood concentrations or biomarkers (e.g. ECG intervals or acetylcholinesterase activity) and how these relate to the time course for that poison, and better prediction of prognosis. This in turn, indicates the appropriate duration of observation and the requirement for some specific treatments. Many specific poisoning treatments aim to favourably alter the pharmacokinetics of the poison. These include activated charcoal, whole bowel irrigation, extracorporeal elimination, chelating agents, antitoxins and urinary alkalinisation. The evidence supporting them, their indications and limitations can only be understood using pharmacokinetic principles. These principles also underpin the appropriate choice within the flexible dosage regimen for many antidotes. In particular, naloxone, flumazenil, methylene blue, atropine and pralidoxime all use variable doses and have an elimination half-life that is much shorter than many (but not all) of the poisons treated by these agents. A firm grounding in pharmacokinetics/toxicokinetics should be regarded as a core competency for all professionals involved in clinical care or undertaking research in clinical toxicology.

Keywords

Central Compartment Peripheral Compartment Molecular Adsorbent Recirculate System Propanil Distribution Kinetic 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

Darren Roberts drafted the manuscript in discussion with Nick Buckley and it was subsequently improved by both authors. Dr Roberts acknowledges the support of the National Health and Medical Research Council (Australia). The South Asian Clinical Toxicology Research Collaboration is funded by Wellcome Trust/National Health and Medical Research Council International Collaborative Research Grant GR071669MA.

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

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Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  1. 1.South Asian Clinical Toxicology Research Collaboration, Medical SchoolAustralian National UniversityCanberraAustralia

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