[Principles and perspectives of clinical pharmacology]

Basic research led to the clarification of the mechanisms of action of numerous pharmacotherapeutic agents. Experimental and clinical pharmacology has a key position in the formulation and introduction of effective and safe medications. The investigation of pharmacokinetic and pharmacodynamic effects must use reproducible quantitative methods, such as controlled clinical trials. However, the complexity of medical, ethical and legal problems inherent in controlled clinical trials may explain why few pharmacological studies have been performed in intensive care medicine conditions. A particular problem is undoubtedly the need for a multimodal treatment, as this might well lead to drug interactions in the critically ill. We generally have to distinguish between pharmacokinetic interactions, i.e. resorption, distribution, altered interaction between metabolism and elimination of a drug, and pharmacodynamic interactions due to synergistic or antagonistic affects at the same receptor or target organ. In recent decades clinical pharmacology has developed in a dualistic manner. Whereas the correlation between plasma level and therapeutic effects is considered to be of primary importance, the correlation between dosage and relevant pharmacodynamic effects is thought to be of only secondary relevance. Pharmacokinetics and pharmacodynamics should not be seen as rival approaches, but rather as complementary methods in clinical pharmacology.