Introduction. Since drug interactions may result in serious adverse effects
or failure of therapy, it is of huge importance that health professionals
base their decisions about drug prescription, dispensing and administration
on reliable research evidence, taking into account the hierarchy of data
sources for evaluation. Clinical Significance of Potential Interactions -
Information Sources. The sources of data regarding drug interactions are
numerous, beginning with various drug reference books. However, they are far
from uniformity in the way of choosing and presenting putative clinically
relevant interactions. Clinical Significance of Potential Interactions -
Interpretation of Information. The difficulties in interpretation of drug
interactions are illustrated through the analysis of a published example
involving assessment made by two different groups of health professionals.
Systematic Evaluation of Drug-Drug Interaction. The potential for
interactions is mainly investigated before marketing a drug. Generally, the
in vitro, followed by in vivo studies are to be performed. The major
metabolic pathways involved in the metabolism of a new molecular entity, as
well as the potential of induction of human enzymes involved in drug
metabolism are to be examined. In the field of interaction research it is
possible to make use of the population pharmacokinetic studies as well as of
the pharmacodynamic assessment, and also the postregistration monitoring of
the reported adverse reactions and other literature data. Conclusion. In
vitro and in vivo drug metabolism and transport studies should be conducted
to elucidate the mechanisms and potential for drug-drug interactions. The
assessment of their clinical significance should be based on well-defined and
validated exposure-response data.
Model-Informed Drug Discovery and Development Strategy for the Rapid Development of Anti-Tuberculosis Drug Combinations
