What is biomedical research
The biomedical research is often referred to as theoretical research due to the missing practical use of drugs, but the research results point to a more fundamental understanding of the mechanisms involved in the actions of the drugs on the organism or the actions of the organism on the drug.
The research is particularly focused on intra- and interindividual differences in pharmacokinetics and pharmacodynamics and within this field, clinical pharmacologists have contributed significantly in the past and will continue to do so in the future. The mechanisms in the variability usually involve inherited or acquired differences in the genes encoding for drug targets, drug transporters and drug metabolizing enzymes. The perspective on the research should not only be in understanding the molecular mechanisms but also in designing geno- or phenotyping tests, which may be applied on forecasting drug response in individual patients.
There are two separate approaches in pharmacokinetic research, one based on several drug measurements in a fixed time schedule in a few subjects and the other being based on a single measurement in each subject of a large population of patients (population pharmacokinetics) and such studies serve to map out the contribution of the different drug metabolizing enzymes, notably cytochrome P450 (CYP) enzymes. The general pharmacokinetic studies are also used to assess the role of drug transporters (eg. P-glycoprotein) for interindividual variability.
Therapeutic drug monitoring (TDM)
TDM is a scientific medical technology where clinical pharmacology has made major contributions. TDM is used to ensure that all patients achieve similar plasma levels of a drug above a certain upper limit for therapeutic failure and below a certain lower level for toxicity through adjustment of the dose. TDM is based on the assumption that the plasma level of the drug reflects the concentration at the drug target, although this may not always be the case. Research in TDM has shown that the technology is of potential usefulness for drugs that have a large pharmacokinetic variability, a narrow therapeutic plasma concentration range and for which dose titration on the basis of clinical or para-clinical measurements is not feasible.
In the past, pharmacokinetic and TDM research in clinical pharmacology focused on certain subgroups of patients at particular risk: the elderly, children and patients with renal or hepatic failure. Following the mapping of the human genome and the revolutionary developments in biotechnology and human molecular medicine, the research in the beginning of the 21st century mainly aims at understanding the role of variations in the coding sequences for drug metabolizing enzymes and transporters for the intra- and interindividual differences in pharmacokinetics and clinical response.
Field of work
The clinical pharmacologist needs to understand the principles of the laboratory methods but may not be able to perform them. The main responsibility of the clinical pharmacologist is to formulate a clinically relevant study problem, to be medically responsible for the volunteers and to translate the results into clinical practice.
The biomedical research in Odense has traditionally focused on tricyclic antidepressants and selective serotonin reuptake inhibitors in relation to genetic polymorphism in CYP, especially CYP2C19 and CYP2D6 and drug-drug interactions. We have also studied the role of CYP2D6 in relation to the analgesic effects of codeine, tramadol and oxycodone. More recently, we have studied the role of genetic variation in genes that are relevant for the transport and oxidation of paclitaxel in patients with ovarian cancer. Future studies involve the pharmacogenetics of metformin in type-2 diabetes mellitus and heroin overdose.