Hall I H, Reynolds D J, Wyrick S D, Maguire J H, Shrewsbury R P
School of Pharmacy, University of North Carolina, Chapel Hill 27514.
Drug Metab Dispos. 1988 Mar-Apr;16(2):196-200.
Disposition studies of the potent experimental hypolipidemic agent, o-(N-phthalimido)acetophenone, were conducted in the laboratory rat. Intravenous administration of the drug demonstrated a declining biphasic plasma concentration-time curve suggesting a rapid distribution into tissues. Less than 5% of the intravenous dose was recovered in urine and feces after 5 days. Oral administration of the drug showed that the maximum blood levels were attained within 15 min. After 48 hr, 92% of the orally administered 14C dose was eliminated either via urine (60%) or feces (40%). 14C in a 0-24-hr urine collection after oral administration showed that urinary radioactivity was composed of 22% of the parent compound o-(N-phthalimido) acetophenone, a benzoic acid metabolite (22%) o-(N-phthalimido)benzoic acid, and an amic acid metabolite (56%) N-(o-acetophenone)phthalamic acid. The two metabolites were unconjugated and possessed less hypolipidemic activity than the parent drug.
在实验大鼠中对强效实验性降血脂药物邻苯二甲酰亚胺基苯乙酮进行了处置研究。静脉注射该药物后，血浆浓度 - 时间曲线呈双相下降，表明药物迅速分布到组织中。5天后，静脉注射剂量中不到5%在尿液和粪便中回收。口服该药物显示，15分钟内达到最高血药浓度。48小时后，口服的14C剂量的92%通过尿液（60%）或粪便（40%）排出。口服给药后0 - 24小时尿液收集的14C显示，尿中放射性由22%的母体化合物邻苯二甲酰亚胺基苯乙酮、一种苯甲酸代谢物（22%）邻苯二甲酰亚胺基苯甲酸和一种酰胺酸代谢物（56%）N - （邻苯乙酮基）邻苯二甲酸组成。这两种代谢物均未结合，且降血脂活性低于母体药物。
