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A cocktail of four model substances orally administered to humans is used for simultaneous characterization of phenobarbital and 3-methylcholanthrene inducible forms of cytochrome-P450 and two genetic polymorphisms, the debrisoquine hydroxylation and N-acetylation. The investigations offer the possibility to assess four main processes of hepatic drug metabolism as well as the judgement of alterations in drug elimination. Both acetylation and hydroxylation phenotypes are not influenced after administration of the cocktail compared to the administration of the substances alone. A statistically significant 30.4% increase of mean body residence time could be found only for monomethylaminoantipyrine. The other pharmacokinetic parameters of monomethylaminoantipyrine and caffeine were unchanged. A one-point-determination for the 9 hour serum concentrations of monomethylaminoantipyrine, caffeine and sulfamethazine/acetylsulfamethazine as well as the 0-9 hours urine concentrations of debrisoquin/4-hydroxydebrisoquin will be conceivable by using "normal ranges".

Comparative studies on binding capacity of some drugs to plasma proteins of newborns and adults were carried out. Plasma from the newborn and adult rabbits as well as human from 4 sources: a) from healthy adults, b) from cord blood, c) from 5 days old newborns, and 6 month old infants were used for the experiments. For methodological reasons in the first part of our studies we have chosen: two sulfonamides - sulfamethazine and sulfamethoxasole, chlorpromazine and sodium salicylate. In the experiments two different techniques were used 1) equilibrium dialysis, 2) ultrafiltration. On the basis of the results obtained in animals as well as in human beings it was noted that the degree of drug binding to plasma proteins in newborns was different from that observed in adults, it may be higher or lower according to the drug used. The knowledge of this fact is of great importance, and should be taken into consideration in the calculation of proper dosage of various drugs in the newborns and infants.

The pharmacokinetic properties of sulphaperine-sodium, Mebacid 200, and sulphadimidine-sodium were experimentally established from fowl and mathematically objectivated. The highest half-life for elimination, coupled with low protein fixation, was recorded from sulphadimidine, by comparison of the above three sulphonamides. These data were used in dosage calculations for clinical testing.