[The bioavailability of orally administered drugs with special regard to the liver as a filter for foreign matter].

A survey of the various aspects of the concept of bioavailability of orally administered drugs is presented. Oral bioavailability may be less than complete as a result of one of three main situations: incomplete absorption due to very slow and/or incomplete dissolution of the drug in the gastrointestinal tract, incomplete absorption due to poor permeability of the drug through the intestinal epithelia, and biotransformation of the drug during its first passage through the liver. This latter so-called first-pass effect is discussed in details. The main clinical concern of a substantial first-pass effect lies in the frequently observed large interindividual variability of the effect. This results in unduly variable drug-concentrations in the blood of patients treated by the same oral standard dosage. The mechanism of this phenomenon is outlined and referred to a shift of the drug metabolising reactions in the liver from first-order type to Michaelis-Menten type during the absorption phase. As to the significance of the oral bioavailability of a drug in human pharmacotherapy, the clinical impact of bioavailability should not be overemphasized. It should rather be judged and considered in the light of the different aspects of the pharmacodynamic potency of the drug. This, however, implies that the physician is acquainted with the main mechanisms involved in the impairment of oral availability.