Pharmacotherapy in shock syndromes: the neglected field of pharmacokinetics and pharmacodynamics.

Promising effects of adjuvant drugs in experimental shock models often are not confirmed in subsequent clinical trials, e.g., steroids, fibronectin, naloxone, immunotherapeutics. A key difficulty in establishing a therapeutic benefit in clinical studies, apart from study design shortcomings, is the lack of knowledge and application of principles of clinical pharmacokinetics and -dynamics. In shock states the relationship between an administered fixed dose regimen and the drug effect is strongly influenced by dynamic changes in absorption, distribution, metabolism, and elimination of the drug, all of which vary between individual patients. This article describes several neglected aspects of clinical pharmacology relevant to shock research under clinical conditions and discusses the indications, prerequisites, and limitations of "applied pharmacokinetics." The inclusion of therapeutic drug monitoring in clinical shock studies should be applied more frequently to establish experimental results in the "real world" of ICU settings.