How do we use drug concentration data to improve the treatment of overdose patients?
The role of drug assays for screening, diagnosis, and guiding treatment decisions in overdose patients remains unclear. The use of drug concentration data in clinical toxicology research is more problematic, with studies using drug concentrations to simply confirm ingestion in observational studies or others report drug concentration time profiles with simplified pharmacokinetics. The reasons for the lack of more substantial pharmacokinetic and/or pharmacodynamic analysis in overdose patients include problems with uncertainty in dose, uncertainty in the time of ingestion, and limited sampling in the absorption phase. Many of these can be overcome by using population pharmacokinetic and pharmacokinetic-pharmacodynamic analysis in prospective studies of overdose patients to understand dose-concentration-effect relationships. Uncertainty in dose and dose time can be included using population analysis techniques, which may involve a clinical assessment of the veracity of the patient history. The pharmacokinetic-pharmacodynamic model can then be used as the basis for predicting toxicity and clinical outcomes from historical information such as dose and early clinical effects. Using such an approach means that the use of drug concentration data in research will improve the risk assessment in overdose patients, without requiring these assays to be rapidly available in the acute health setting.
Isbister
Geoffrey K
GK
Department of Clinical Toxicology and Pharmacology, University of Newcastle, New South Wales, Australia. geoff.isbister@gmail.com
D002986:Clinical Trials as Topic; D062787:Drug Overdose; D006801:Humans; D004364:Pharmaceutical Preparations; D010599:Pharmacokinetics; D044382:Population Groups / Q000706:statistics & numerical data*; D018570:Risk Assessment
D004364:Pharmaceutical Preparations