Research Projects

The action of a drug is affected by its distribution and disposition in the body. Taking anticancer drugs as an example, it is well known that those which can kill cancer cells in the test-tube do not necessarily exhibit satisfactory antitumor effects when given to patients. This is because the anticancer drugs also distribute to normal cells, producing a variety of adverse effects before the tumor cells are completely destroyed. Consequently, major advances in drug therapy can be expected if drug delivery systems (DDS) can be developed to control disposition in the body and selectively attack target tissues. The development of ideal DDS is the ultimate goal of our research and, at present, work is in progress to examine the major factors which govern drug disposition in the body and to clarify the mechanisms involved inf membrane transport in the liver, brain, kidney, intestine and the tumor itself. In the life sciences, research normally starts at the body (in vivo) level and progresses to the organ, cell, protein and gene level in order to understand the principles involved in the functions of the human body. Such an approach has met with a great deal of success. However, "the prediction and control of drug effects and safety" will never be fully achieved unless we develop methodology to reconstruct quantitatively in vivo phenomena from in vitro data. Before drugs can exert their ultimate effects they have to undergo a variety of different processes: (1) absorption from the site of administration to reach the circulating blood, (2) detoxification via metabolism and excretion, (3) distribution to the tissue(s) involved in their pharmacological (or adverse) effects and (4) binding to pharmacological receptors, followed by signal transduction etc. It is possible to describe these processes using physiological and anatomical parameters such as blood flow, tissue volume, pH and the membrane potential difference between the outside and inside of the cells as well as biochemical parameters representing drug binding to blood and tissue macromolecules, membrane permeability, interaction with metabolic enzymes, transport carriers and pharmacological and toxicological receptors and acceptors. Indeed, by incorporating such physiological and biochemical parameters into appropriate mathematical models, we have been attempting to predict the output "exertion of pharmacological and adverse effects" from the input "dose of drug, route of administration and pathophysiological condition of the patients". The research project now underway can be divided into seven areas as described left.