Hultin T A, Filla M S, McCormick D L
Life Sciences Research, IIT Research Institute, Chicago, IL 60616.
Drug Metab Dispos. 1990 Mar-Apr;18(2):175-9.
The metabolism and disposition of N-(4-methoxyphenyl)-all-trans-retinamide (MPR), the major metabolite of N-(4-hydroxyphenyl)-all-trans-retinamide (4-HPR), were investigated in female B6D2F1 (BDF) mice. Following a single oral dose of 10 mg/kg, MPR distributed to the serum, liver, mammary gland, urinary bladder, and skin. The highest levels of MPR were detected in the liver and mammary gland, and the largest values for AUC were in the mammary gland followed by the skin and liver. The t1/2 for MPR was 5.1 hr in liver, 5.6 hr in serum, 18.7 hr in urinary bladder, 23.1 hr in skin, and 26.6 hr in mammary gland. MPR and five metabolites were detected; levels varied between tissues. One metabolite was 4-HPR; the other four, which eluted at 7, 12, 13, and 18 min, remain unidentified. The major metabolite of MPR was the 18-min metabolite and comprised 17% of total retinoid in skin and 14% in mammary gland. 4-HPR was only a minor metabolite of MPR; 4-HPR was not detectable in serum or urinary bladder and accounted for less than 4% of total retinoid in the other tissues. In mice dosed with 10 mg/kg 4-HPR, the parent compound, MPR, a putative 4-HPR ester, and three of the MPR metabolites (7, 13, and 18 min) were found. These data suggest that the interconversion of 4-HPR and MPR greatly favors formation of MPR.(ABSTRACT TRUNCATED AT 250 WORDS)
在雌性B6D2F1（BDF）小鼠中研究了N-（4-羟基苯基）-全反式维甲酸（4-HPR）的主要代谢产物N-（4-甲氧基苯基）-全反式维甲酸（MPR）的代谢和处置情况。单次口服剂量为10mg/kg后，MPR分布于血清、肝脏、乳腺、膀胱和皮肤。肝脏和乳腺中检测到的MPR水平最高，AUC的最大值出现在乳腺，其次是皮肤和肝脏。MPR在肝脏中的t1/2为5.1小时，在血清中为5.6小时，在膀胱中为18.7小时，在皮肤中为23.1小时，在乳腺中为26.6小时。检测到MPR及其五种代谢产物；各组织中的水平有所不同。一种代谢产物是4-HPR；其他四种在7、12、13和18分钟洗脱的代谢产物仍未鉴定。MPR的主要代谢产物是18分钟时出现的代谢产物，在皮肤中占总类视黄醇的17%，在乳腺中占14%。4-HPR只是MPR的次要代谢产物；血清或膀胱中未检测到4-HPR，在其他组织中占总类视黄醇的比例不到4%。在给予10mg/kg 4-HPR的小鼠中，发现了母体化合物、MPR、一种假定的4-HPR酯以及MPR的三种代谢产物（7、13和18分钟时出现的代谢产物）。这些数据表明，4-HPR和MPR的相互转化极大地有利于MPR的形成。（摘要截断于250字）
