Relation Between the Molecular Structure of a Drug and its Photobiological Activity by Combination of In vivo and In vitro Research

Abstract

The in vivo situation is very complex and information about the molecular mechanism underlying a photobiologic response is hardly gained by in vivo investigations only. Therefore in vitro experiments are performed. However, there are problems with extrapolating in vitro results to processes occurring in the whole animal. The reason is that in vitro research is based on models of the in vivo situation and as a result the information obtained, although abundant, often lacks the desired relevance by neglecting important parameters such as metabolism and bioavailability of a drug. Answering the question how to extrapolate in vitro results to the in vivo situation can be circumvented as follows: As the photobiologic effect to be studied is an in vivo problem, in vitro investigations should be continuously performed in close harmony with in vivo research; conclusions from in vitro research need verification in the in vivo system. A photobiologic problem can be solved efficiently if in vitro and in vivo research are in continuous interaction with each other. This means that the (experimental) approach to the problem, at any of both sides, is guided by results from the other side. Such an integration of in vitro and in vivo research was tried out with some imino-Noxides. (Aim of the research was to find the part of the molecular structure responsible for phototoxic/photo-allergic effects. This gives the opportunity to alter the structure in such a way that the phototoxicity diminishes, whereas desired, pharmacological effects are conserved.)