Honig P K, Smith J E, Wortham D C, Zamani K, Cantilena L R
Department of Pharmacology, Uniformed Services University of the Health Sciences Bethesda, Maryland 20814-4799, USA.
Drug Metabol Drug Interact. 1994;11(2):161-8. doi: 10.1515/dmdi.1994.11.2.161.
Terfenadine is nearly completely first pass biotransformed. Unmetabolized terfenadine plasma concentrations have been associated with altered cardiac repolarization. During previous drug interaction studies, 2 subjects were found to have quantifiable concentrations of unmetabolized terfenadine with accompanying electrocardiographic repolarization changes while on terfenadine alone. To determine whether these subjects were representative of the population, 150 healthy volunteers (109 males, 41 females, ages 19-49) were screened for their ability to metabolize terfenadine after achieving steady-state. Blood was obtained at known times of maximum terfenadine concentration after dosing. Eleven subjects had quantifiable concentrations of terfenadine demonstrating wide intersubject variability in terfenadine metabolism. Further studies to determine whether such subjects are more susceptible to untoward terfenadine-associated events are underway.
特非那定几乎完全经首过生物转化。未代谢的特非那定血浆浓度与心脏复极改变有关。在先前的药物相互作用研究中，发现有2名受试者在单独服用特非那定时，未代谢的特非那定浓度可被定量检测到，同时伴有心电图复极变化。为了确定这些受试者是否代表总体人群，对150名健康志愿者（109名男性，41名女性，年龄19 - 49岁）在达到稳态后进行了特非那定代谢能力筛查。在给药后已知的特非那定浓度峰值时间采集血液。11名受试者的特非那定浓度可被定量检测到，这表明特非那定代谢存在广泛的个体间差异。关于此类受试者是否更易发生与特非那定相关的不良事件的进一步研究正在进行中。
