Lautenschlager M T, Viktor S, Müller U A, Hoffmann A
Institut für Klinische Pharmakologie, Friedrich-Schiller-Universität, Jena, Germany.
Pharmazie. 1996 Oct;51(10):750-3.
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.
将四种物质的混合物(咖啡因/CYP1A/CYP1A2、安乃近/CYP2B、异喹胍/CYP2D6和磺胺二甲嘧啶/N-乙酰转移酶)在胰岛素治疗(IT)前和治疗6个月后给予15名成年起病的糖尿病患者,以研究病理状态下人体肝脏生物转化能力的变化。口服药物6小时后采集血液和尿液样本。在胰岛素治疗前或治疗期间,乙酰化和羟化表型没有差异。然而,胰岛素治疗期间游离磺胺二甲嘧啶浓度的显著增加可解释为代谢控制不佳导致N-乙酰转移酶的诱导。咖啡因浓度的比较没有显著差异。显然,在人类中CYP1A2不受II型糖尿病的影响。安乃近的代谢产物4-甲基安替比林(4-MAA)的浓度在胰岛素治疗期间显著增加。这一结果表明代谢控制不佳可能诱导CYP2B。