Chronopharmacology and Therapeutic Drug Regulations: Commentary

A quiet, little-publicized development has taken place in the biomedical sciences in recent years. The new terms chronobiology, chronopharmacology, chronopharma-codynamics, chronopharmacokineties, and even chronotoxicology very gently have entered our language and our science. Chronobiologic considerations have been proved to increase or decrease therapeutic drug effectiveness or modify their toxicology. Many authors have pointed out that cues to these advantages or disadvantages may be obtained from animal studies that show that normal changes of cellular rhythms take place at prescribed intervals for many biologic parameters. We are observing replacement of the traditional unidimensional reference intervals by timing drug administration most effectively according to the rhythms having phase, frequency, and amplitude. Oncologists have utilized these concepts most successfully to increase the therapeutic effectiveness and decrease toxicity of antineoplastic agents. In addition, asthma has received great attention as a circadian rhythm-related disorder; angina and myocardial infarction, hypertension, peptic ulcer, and epilepsy are other disease conditions that have been treated successfully by understanding how biological rhythms influence diagnosis and therapy.