The Concept of Conditional Pharmacology and Toxicology

Abstract

The concept of conditional pharmacology as initially elucidated by Dr Michael Whitehouse and his colleagues from their studies of drug-disease interactions has broad import in a rational drug discovery and development programme. The concept can be extended to toxicology and thus can be viewed as encompassing virtually all means and methods of discovering and enhancing the efficacy, while reducing the toxicity of drugs and biologics. The concept involves employing the physiological or metabolic activity, genetic and/or molecular structure of the host, of the disease process and/or of the parasite to activate and target the drug or biologic, as well as to regulate and delimit its activity. Thus, the concept not only applies to the treatment of inflammatory diseases, but also to the treatment of neoplastic and infectious diseases, to facilitating wound healing, and is in fact an underlying assumption, and expected consequence, of successful gene therapy. The concept applies to clinical studies as well, arguing for more pharmacokinetic and chrono-pharmacological studies in the early phases of clinical testing and the inclusion in later-stage clinical trials of more diverse populations, as regards age, gender and ethnicity, if the indication warrants. Facilitating and monitoring compliance, post- as well as pre-market approval, also are critical components of the fully implemented concept.