E‐ and Z‐10‐hydroxylation of nortriptyline: Relationship to polymorphic debrisoquine hydroxylation
E‐ and Z‐10‐hydroxylation of nortriptyline: Relationship to polymorphic debrisoquine hydroxylation
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去甲替林的 E-和 Z-10-羟基化：与多晶型异喹啉羟基化的关系
DOI：
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发表时间：
1981
期刊：
影响因子：
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通讯作者：
F. Sjöqvist
中科院分区：
文献类型：
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作者：
B. Mellström;L. Bertilsson;J. Säwe;Hans;F. Sjöqvist
选择8名健康受试者[使用异喹胍（D）羟基化试验进行表型分型]，以涵盖尿液中D和4-羟基异喹胍（4-OH-D）之间的广泛比例。去甲替林（NT）单次口服给药后，E-位（而非Z-位）10-羟基化的代谢清除率与代谢比D/4-OH-D密切相关（rs =-0.88，p < 0.01）。这表明共同的酶机制参与D和E-的羟基化，但不参与NT的Z-10-羟基化。NT和D的缓慢羟化酶在尿液中排泄的10-羟基去甲替林较少，NT的血浆清除率低于快速羟化酶。NT的总血浆清除率与E-10-羟基化代谢清除率之间的强相关性（r = 0.96）表明，该代谢反应在药物处置中很重要。
Eight healthy subjects [who were phenotyped with a debrisoquine (D) hydroxylation test] were selected to cover a wide range in the ratio between D and 4‐hydroxydebrisoquine (4‐OH‐D) in the urine. After a single oral dose of nortriptyline (NT) the metabolic clearance by 10‐hydroxylation in the E‐position, but not in the Z‐position, correlated closely to the metabolic ratio D/4‐0H‐D (rs = ‐0.88, p < 0.01). This indicates that common enzymatic mechanisms are involved in the hydroxylation of D and the E‐ but not the Z‐10‐hydroxylation of NT. Slow hydroxylators of NT and D excreted less 10‐hydroxynortriptyline in urine and had lower plasma clearance of NT than the rapid hydroxylators. The strong correlation (r = 0.96) between the total plasma clearance of NT and the metabolic clearance by E‐10‐hydroxylation shows that this metabolic reaction is important in the disposition of the drug.