Mellström B, Bertilsson L, Säwe J, Schulz H U, Sjöqvist F
Clin Pharmacol Ther. 1981 Aug;30(2):189-93. doi: 10.1038/clpt.1981.147.
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-OH-D (rs = -0.88, p less than 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.
选取了8名健康受试者[通过异喹胍（D）羟基化试验进行表型分析]，以涵盖尿液中D与4 - 羟基异喹胍（4 - OH - D）比值的广泛范围。单次口服去甲替林（NT）后，E位而非Z位的10 - 羟基化代谢清除率与代谢比值D/4 - OH - D密切相关（rs = -0.88，p小于0.01）。这表明D的羟基化与NT的E - 10 - 羟基化而非Z - 10 - 羟基化涉及共同的酶促机制。NT和D的慢羟基化者尿液中排泄的10 - 羟基去甲替林较少，且NT的血浆清除率低于快羟基化者。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，这种代谢反应在药物处置中很重要。
