[Problems in dose finding from the view of the clinical pharmacologist (author's transl)].

The dose of a drug applied to a patient is determined by his physiological and pathological data, by specific properties of the drug and by the mode of application. The most important physiological data which influence the dose are body weight, sex, age, a pregnancy, genetic variations and circadian rhythm. Pathological findings such as organ insufficiencies (kidneys, heart, liver, endocrinium, transport protein in the blood, etc.) are also to be considered. Particularities of the drug kinetics (insignificant absorption, excessive biological half-life, specific affinities to tissues, etc.), of metabolism (first-pass effect, toxic metabolites, saturable detoxification, stress, etc.) or a high toxicity are other parameters of consequence. Finally attention has to be paid to the mode of application (p.o., i.v., etc.), to the kind of galenic preparation (liquid or solid, slow-releasing preparation, etc.), to interactions if using combinations of drugs and to a long-lasting pharmacotherapy. Aditional problems are encountered in clinical trials especially in early phases while determining the tolerable therapeutic dose.