[Assessment of biotransformation capacity following oral administration of various model substances as cocktail].
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".
Henschel
L
L
Institut für Klinische Pharmakologie der FSU, Jena.
Hoffmann
A
A
D000107:Acetylation; D000284:Administration, Oral; D000328:Adult; D001711:Biotransformation; D002110:Caffeine / Q000008:administration & dosage / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D003647:Debrisoquin / Q000008:administration & dosage / Q000378:metabolism*; D004177:Dipyrone / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D006900:Hydroxylation; D008099:Liver / Q000378:metabolism*; D008297:Male; D010641:Phenotype; D013418:Sulfamethazine / Q000008:administration & dosage / Q000378:metabolism*
D002110:Caffeine; D013418:Sulfamethazine; D004177:Dipyrone; D003577:Cytochrome P-450 Enzyme System; D003647:Debrisoquin
Einschätzung der Biotransformationskapazität nach oraler Gabe unterschiedlicher Modellsubstanzen als "Cocktail".