The dose-related reference range – a new tool for therapeutic drug monitoring (TDM)

In former years it was generally accepted to use therapeutic drug monitoring (TDM) to prevent toxic side effects of drugs with a narrow therapeutic window. Very often it was just used to confirm that a side effect that had already occurred was due to an elevated drug plasma concentration. For this purpose the quantified drug concentration was related to the therapeutic reference range of the drug. We relate the drug concentration to both the therapeutic reference range and the dose-related reference range. Dose-related reference ranges are calculated according to the mathematical equation De = Clt * c, where De is the maintenance dose and Clt the total clearance taken as x ± SD from phase II trials of the drug. A drug concentration outside this range is taken as a signal that the patient does not belong to the study population because of a comedication or a pharmacologically active food or drug component (drug-drug-interaction), an age below 18 years (children), an age above 65 years (old people), a genetically determined alteration in drug metabolism (fast/slow metabolizers), diseases in the elimination organs, or non-compliance. KONBEST, an internet platform that is programmed to allow clinical pharmacological commenting of drug concentrations in TDM, contains the relevant pharmacological data to calculate among others the dose-related reference ranges. By this approach we are able to prevent adverse drug reactions before the drug concentration is high enough to cause them.