Summary

Abstract

On the 4th and 5th of March, 1977, a colloquium was held in the Prince Electorate Castle in Mainz, West Germany, on new experimental and clinical tests on Na-4-hydroxybutyrate (a sodium salt of the y-hydroxybutyric acid Somsanit 4-HB). R. FREY (Mainz) conducted the colloquium. After the numerous guests were welcomed and a brief historical reminiscence concerning 4-HB was represented, the morning session was opened with W. HELLER (Tübingen) as chairman. E. van der KLEIJN (Nijmegen, Holland) presented a very detailed paper “The Concept of Capacity-Limited Elimination of 4-Hydroxybutyrate”, which analyzed the unusually structured pharmacokinetic profiles seen in experiments with 4-HB on laboratory animals. While the elimination of drugs usually follows an exponential pattern characterized either by a straight line or a multiphased line that can be split into two or more degrees in the logarithmics system of concentrationtime values, the elimination of 4-HB always describes a concave curve before ending in a straight line. This phenomenon can be observed in dogs and in man. With the aid of mathematical formulas and logical models, van der KLEIJN discussed and interpreted in detail the relationship existing between enzyme capacity and drug dosage. The pharmacokinetic profile of 4-HB was shown to have a mean Km value of + 90 mg/liter and a Vmax value of 135 mg/h. The concentration at which the patient awakens is rather constant at 90 mg/liter. The elimination profile is directly proportional to the concentration, i. e., the higher the dosage of 4-HB, the longer it takes to be eliminated. Of clinical importance is the fact that elimination is directly dependent on enzyme capacity. For sedation, only a low concentration is necessary, and for anesthesia, a proportionately higher dose. During the following discussion., it was pointed out that 4-HB is eliminated quantitatively, leaves no toxic residue in the organism, and can therefore be viewed as an effective and harmless substance.