The dose makes the medicine.
Dose and time considerations in the development and use of a drug are important for assessing actions and side effects, as well as predictions of safety and toxicity. This article deals with epistemological aspects of dose selection by probing into the linguistic and cultural roots for the measure of medicine mediated by the medical doctor. Because toxicity is related to dose, historic and recent views suggest that less can be more. At low, medium and high dose levels, effects can differ not only quantitatively but also qualitatively. Dose-related target activation and recognition of enantiodromic thresholds between beneficial and toxic effects require elucidation of underlying events. Such studies, including hormesis and microdosing, call for extended ADME procedures with high-resolution methods in addition to the current low-resolution approaches. Improved information of drug logistics and target pharmacokinetics enables effective drug selection, dose determination and prediction. It also allows considerations of systems biology [i.e. integral (gestalt) pharmacology] exemplified by the drug homunculus, as in the case of vitamin D, that might lead to new paradigms and drug design.
Stumpf
Walter E
WE
University of North Carolina at Chapel Hill and International Institute of Drug Distribution, Cytopharmacology and Cytotoxicology, 2612 Damascus Church Road, Chapel Hill, NC 27516, USA. stumpfwe@email.unc.edu
D000818:Animals; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D049490:Systems Biology; D014807:Vitamin D / Q000008:administration & dosage / Q000009:adverse effects
D004364:Pharmaceutical Preparations; D014807:Vitamin D