Levy M, Safadi R, Zylber-Katz E, Granit L, Caraco Y
Department of Medicine, Hadassah University Hospital, Jerusalem, Israel.
Eur J Clin Pharmacol. 2001 Sep;57(6-7):461-5. doi: 10.1007/s002280100341.
We previously found that, compared with healthy subjects. asymptomatic hepatitis-B virus (HBV) carriers displaying slow acetylator phenotype demonstrate a significant prolongation of the elimination half-life of 4-methylaminoantipyrine (MAA) and a decrease in the clearance of formation of 4-aminoantipyrine (AA) and 4-formylaminoantipyrine (FAA). However, the formation of 4-acetylaminoantipyrine (AAA) was unchanged. The present study was designed to examine the effect of the asymptomatic HBV carrier state on the metabolism of dipyrone. as a model drug, in rapid acetylators.
The plasma and urine concentrations of the metabolites of dipyrone were measured in eight asymptomatic HBV carriers and eight healthy subjects who had normal liver function tests, all displaying the rapid acetylation phenotype and genotype, after the administration of a 1.0-g oral dose of dipyrone.
The following pharmacokinetic parameters were evaluated: peak plasma concentration, time to peak plasma concentration, elimination rate constant, area under the plasma concentration-time curve (0-->infinity), amount excreted (0-->infinity), renal and non-renal clearances for MAA and the clearances of formation for AA, FAA and AAA. No significant differences were found between the two subject groups.
The effect of hepatic viral carrier state on drug metabolism may vary according to metabolic pathways and genetic polymorphism.
我们先前发现，与健康受试者相比，表现出慢乙酰化表型的无症状乙型肝炎病毒（HBV）携带者4-甲基氨基安替比林（MAA）的消除半衰期显著延长，4-氨基安替比林（AA）和4-甲酰氨基安替比林（FAA）的生成清除率降低。然而，4-乙酰氨基安替比林（AAA）的生成未发生变化。本研究旨在检测无症状HBV携带者状态对作为模型药物的安乃近在快乙酰化者体内代谢的影响。
在8例无症状HBV携带者和8例肝功能检查正常的健康受试者（均表现为快乙酰化表型和基因型）口服1.0 g安乃近后，测定其血浆和尿液中安乃近代谢物的浓度。
评估了以下药代动力学参数：血浆峰浓度、达血浆峰浓度时间、消除速率常数、血浆浓度-时间曲线下面积（0→∞）、排泄量（0→∞）、MAA的肾清除率和非肾清除率以及AA、FAA和AAA的生成清除率。在两组受试者之间未发现显著差异。
肝脏病毒携带者状态对药物代谢的影响可能因代谢途径和基因多态性而异。
