Grant: CIHR/Regional Partnership Program/Operating Grants

Medication is the most relied-upon treatment in health care today. Despite its importance, the current medication-use system suffers from problems related to lack of safety and quality. In order to understand therapeutic and toxic effects of drugs and to continue developing more selective and effective treatments, analysis of drugs in biological samples and pharmaceutical products is growing in importance. Easy determination of unbound and total concentrations of drugs in biological samples is very important for separating population pharmacokinetics from population pharmacodynamics. Altered plasma protein binding is expected in uremia, liver diseases, after surgery, or when displacing drugs are also administered. In these cases, the target total drug concentration should be adjusted to attain the same therapeutically important unbound concentration. The composition of plasma can be subject to considerable differences due to pathological and non-pathological influences. For example, plasma albumin can be decreased to about 50% of the normal level in hepatic diseases and the concentration of lipoprotein-bound triglycerides depends on dietary status. Accordingly, good therapeutic practice should incorporate methods for determination of both free and total drug concentrations, as well as the concentration of drug binding proteins. Since as many as 70 to 80% of adverse drug reactions are dose related, our success in preventing these adverse reactions is contingent on our ability to conveniently measure drug levels in biological samples, which provides the scientific basis for dose selection. This research will also expand our understanding about the action of medicinal drugs and will speed up the development of new active compounds. Furthermore, the proposed research will improve personal health by increasing the safety of medication for all age groups.