[Comparison of serum concentrations of caffeine, 4-methylaminoantipyrine, sulfamethazine and debrisoquin following oral administration of these substances as a cocktail in type II diabetics before and after insulin therapy].
A cocktail of 4 substances (caffeine/CYP1A/CYP1A2, metamizol/CYP2B, debrisoquin/CYP2D6 and sulfamethazine/N-acetyltransferase) was administered to 15 maturity-onset diabetics before and 6 months after insulin therapy (IT) to examine changes in hepatic biotransformation capacity in humans under pathological conditions. Blood and urine samples were taken 6 h after oral administration of the drugs. There were no differences in acetylation- and hydroxylationsphenotyping before or during IT. However, a significant increase in concentration of free sulfamethazine during IT can be interpreted as induction of N-acetyltransferase by poor metabolic control. Comparison of caffeine-concentration showed no significant differences. Obviously in humans CYP1A2 is not influenced by type-II-diabetes mellitus. Concentration of 4-methyl-antityprine (4-MAA), a metabolite of metamizol, was significantly increased during IT. This results shows a possible induction of CYP2B by poor metabolic control.
Lautenschlager
M T
MT
Institut für Klinische Pharmakologie, Friedrich-Schiller-Universität, Jena, Germany.
Viktor
S
S
Müller
U A
UA
Hoffmann
A
A
D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D002110:Caffeine / Q000008:administration & dosage / Q000493:pharmacokinetics; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000493:pharmacokinetics; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003647:Debrisoquin / Q000008:administration & dosage / Q000493:pharmacokinetics; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D004177:Dipyrone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D047069:Pyrazolones; D013418:Sulfamethazine / Q000008:administration & dosage / Q000493:pharmacokinetics; D013565:Sympatholytics / Q000008:administration & dosage / Q000493:pharmacokinetics
D000890:Anti-Infective Agents; D000697:Central Nervous System Stimulants; D004338:Drug Combinations; D007004:Hypoglycemic Agents; D007328:Insulin; D007527:Isoenzymes; D047069:Pyrazolones; D013565:Sympatholytics; D002110:Caffeine; D013418:Sulfamethazine; D004177:Dipyrone; D003577:Cytochrome P-450 Enzyme System; C008667:noramidopyrine; D003647:Debrisoquin