Hultin T A, McCormick D L, May C M, Moon R C
Life Sciences Research, IIT Research Institute, Chicago, IL 60616.
Drug Metab Dispos. 1988 Nov-Dec;16(6):783-8.
The effects of pretreatment with N-(4-hydroxyphenyl)-all-trans-retinamide (4-HPR) and phenobarbital (PB) on the distribution and metabolism of 4-HPR, and on the levels of hepatic cytochromes, were investigated in female BDF mice. Pretreatment of mice for 3 days with 10 mg/kg 4-HPR had no effect on the disposition of 4-HPR in the serum, liver, mammary gland, or urinary bladder. 4-HPR pretreatment also had no effect on the pharmacokinetics of any of its metabolites in the liver, or on the levels of hepatic cytochromes P450 or b5. By contrast, pretreatment of mice for 3 days with 80 mg/kg PB had a significant effect on the disposition of 4-HPR in all the tissues examined; the areas under the concentration-time curves for PB-pretreated mice were half those for vehicle-pretreated mice. PB pretreatment also significantly reduced the levels of four metabolites of 4-HPR in the liver and increased the levels of hepatic cytochromes P450 and b5. These data suggest that prior or concomitant administration of drugs that induce the mixed function oxidase system could result in changes in retinoid disposition and metabolism; such changes may alter retinoid chemopreventive activity.
在雌性BDF小鼠中研究了用N-(4-羟基苯基)-全反式维甲酸（4-HPR）和苯巴比妥（PB）预处理对4-HPR的分布和代谢以及肝细胞色素水平的影响。用10mg/kg 4-HPR对小鼠预处理3天，对4-HPR在血清、肝脏、乳腺或膀胱中的分布没有影响。4-HPR预处理对其在肝脏中任何代谢物的药代动力学或肝细胞色素P450或b5的水平也没有影响。相比之下，用80mg/kg PB对小鼠预处理3天对4-HPR在所检测的所有组织中的分布有显著影响；PB预处理小鼠的浓度-时间曲线下面积是溶剂预处理小鼠的一半。PB预处理还显著降低了肝脏中4-HPR四种代谢物的水平，并增加了肝细胞色素P450和b5的水平。这些数据表明，预先或同时给予诱导混合功能氧化酶系统的药物可能导致类视黄醇分布和代谢的变化；这种变化可能改变类视黄醇的化学预防活性。
