Levy M, Leibowich I, Zylber-Katz E, Ilan Y, Granit L, Sviri S, Caraco Y
Clinical-Pharmacological Unit, Hadassah University Hospital, Jerusalem, Israel.
Clin Pharmacol Ther. 1997 Jul;62(1):6-14. doi: 10.1016/S0009-9236(97)90145-4.
The pharmacokinetics of a number of drugs has been shown to be impaired in patients with acute or chronic viral liver disease.
To examine the effect of the asymptomatic hepatitis B virus carrier state on the metabolism of dipyrone (INN, metamizole) as a model drug.
The pharmacokinetics of the metabolites of dipyrone-4-methylaminoantipyrine, 4-aminoantipyrine, 4-formylaminoantipyrine, and 4-acetylaminoantipyrine-after a 1.0 gm oral dose of dipyrone were evaluated in nine asymptomatic carriers of hepatitis B virus with normal liver function tests and nine healthy subjects. All subjects displayed the slow acetylator phenotype.
The nonrenal (metabolic) clearance of 4-methylaminoantipyrine was significantly reduced (mean +/- SEM) (123.3 +/- 15.8 versus 182.9 +/- 15.1 ml.min-1, respectively; p < 0.02) in the carriers of hepatitis B virus compared with the healthy subjects, and the elimination half-life of this metabolite was significantly longer (3.69 +/- 0.35 versus 2.64 +/- 0.28 hours, respectively; p < 0.03). The formation clearances of 4-aminoantipyrine and 4-formylaminoantipyrine were significantly smaller in the carriers of hepatitis B virus compared with healthy subjects (33.8 +/- 6.2 versus 55.2 +/- 6.4 ml.min-1; p < 0.03, and 16.7 +/- 2.2 versus 34.2 +/- 4.2 ml.min-1; p < 0.002; respectively). However, the elimination half-life of 4-formylaminoantipyrine was found to be slightly shorter in the carriers of hepatitis B virus. No significant differences were noted between the groups in the pharmacokinetics of 4-acetylaminoantipyrine.
The metabolism of dipyrone is impaired in asymptomatic carriers of hepatitis B virus. Clinically latent infection with hepatitis B virus seems to exert a differential effect on metabolism of the drug. Oxidative pathways to produce 4-aminoantipyrine and 4-formylaminoantipyrine were significantly affected, whereas acetylation remained intact. This study provided an additional example of the effect of a virus on the disposition of a drug.
多项研究表明，急慢性病毒性肝病患者体内多种药物的药代动力学受到影响。
以安乃近（国际非专利药品名称，甲氨基安替比林）作为模型药物，研究无症状乙肝病毒携带者状态对其代谢的影响。
选取9名肝功能检查正常的无症状乙肝病毒携带者和9名健康受试者，给予他们口服1.0克安乃近后，评估其代谢产物4-甲基氨基安替比林、4-氨基安替比林、4-甲酰氨基安替比林和4-乙酰氨基安替比林的药代动力学。所有受试者均表现为慢乙酰化表型。
与健康受试者相比，乙肝病毒携带者体内4-甲基氨基安替比林的非肾（代谢）清除率显著降低（均值±标准误）（分别为123.3±15.8与182.9±15.1毫升·分钟-1；p<0.02），且该代谢产物的消除半衰期显著延长（分别为3.69±0.35与2.64±0.28小时；p<0.03）。与健康受试者相比，乙肝病毒携带者体内4-氨基安替比林和4-甲酰氨基安替比林的生成清除率显著降低（分别为33.8±6.2与55.2±6.4毫升·分钟-1；p<0.03，以及16.7±2.2与34.2±4.2毫升·分钟-1；p<0.002）。然而，发现乙肝病毒携带者体内4-甲酰氨基安替比林的消除半衰期略短。两组之间4-乙酰氨基安替比林的药代动力学未观察到显著差异。
无症状乙肝病毒携带者体内安乃近的代谢受到损害。乙肝病毒的临床潜伏感染似乎对该药物的代谢产生不同影响。生成4-氨基安替比林和4-甲酰氨基安替比林的氧化途径受到显著影响，而乙酰化过程保持完整。本研究为病毒对药物处置的影响提供了又一实例。
