Wu Wu-Nan, McKown Linda A, Reitz Allen B
Johnson & Johnson Pharmaceutical Research & Development, LLC, Spring House, PA 19477, USA.
Eur J Drug Metab Pharmacokinet. 2007 Jul-Sep;32(3):171-6. doi: 10.1007/BF03190479.
The in vivo metabolism of the antipsychotic agent mazapertine was studied after oral administration of mazapertine succinate (40 mg/subject) to two healthy volunteers, and urine (0-24 hours) was obtained for metabolite identification using API-ionspray LC/MS and MS/MS analysis. Unchanged mazapertine (12% of the sample) plus 10 metabolites were profiled, quantified, and tentatively identified on the basis of MS data, Glusulase-hydrolysis, and by comparison to synthetic samples. The formation of mazapertine metabolites are via seven metabolic pathways: (1) phenylhydroxylation, (2) piperidyl oxidation, (3) O-dealkylation, (4) N-dephenylation, (5) oxidative N-debenzylation, (6). depiperidylation, and (7) glucuronidation. Pathways 1, 2, 5 and 7 formed 4-OH-phenyl-mazapertine (M1, 18%) and 4-OH-piperidyl (M2, 14%)-mazapertine, carboxybenzoylpiperidine (M8, 10%) and its glucuronide (M9, 14%) as four major metabolites. Six moderate and minor metabolites (M3-M7 & M10; each < or =10%) formed via a combination of pathways 1-6. Mazapertine is extensively metabolized in humans.
在向两名健康志愿者口服琥珀酸马扎哌汀（40毫克/受试者）后，研究了抗精神病药物马扎哌汀的体内代谢情况，并收集尿液（0 - 24小时），使用API离子喷雾液相色谱/质谱联用仪和串联质谱分析法进行代谢物鉴定。基于质谱数据、葡糖淀粉酶水解以及与合成样品的比较，对未变化的马扎哌汀（占样品的12%）以及10种代谢物进行了分析、定量和初步鉴定。马扎哌汀代谢物的形成通过七种代谢途径：（1）苯基羟基化，（2）哌啶基氧化，（3）O - 去烷基化，（4）N - 去苯基化，（5）氧化N - 去苄基化，（6）去哌啶化，以及（7）葡萄糖醛酸化。途径1、2、5和7形成了4 - 羟基苯基 - 马扎哌汀（M1，18%）、4 - 羟基哌啶基（M2，14%） - 马扎哌汀、羧基苯甲酰哌啶（M8，10%）及其葡萄糖醛酸苷（M9，14%）这四种主要代谢物。六种中度和轻度代谢物（M3 - M7和M10；每种均≤10%）通过途径1 - 6的组合形成。马扎哌汀在人体内被广泛代谢。
