Roy S D, Hawes E M, Midha K K
J Pharm Sci. 1987 Jun;76(6):427-32. doi: 10.1002/jps.2600760603.
The disposition of methoxyphenamine (o-methoxy-N,alpha-dimethylphenethylamine) and three of its metabolites was studied in five healthy volunteers on three occasions, with the urine pH separately under uncontrolled, acidic, and basic conditions. All five volunteers were extensive metabolizers of debrisoquine and methoxyphenamine, the latter with respect to O-demethylation and aromatic 5-hydroxylation. The plasma peak concentration and the area under the curve of methoxyphenamine from 0 to infinity did not differ significantly during the three phases of the study. However, on the average, its renal clearance increased by fivefold and its plasma terminal half-life decreased by twofold in the acidic as compared with the alkaline urine condition. The urinary excretions of methoxyphenamine and its metabolites N-desmethylmethoxyphenamine and O-desmethylmethoxyphenamine were significantly enhanced in the uncontrolled pH and the acidic urine conditions as compared with the alkaline urine condition. By contrast, the urinary excretion of the 5-hydroxymethoxyphenamine metabolite was not significantly affected by urinary pH variations. The mean urinary excretion ratios methoxyphenamine: O-desmethylmethoxyphenamine and N-desmethylmethoxyphenamine: O-desmethylmethoxyphenamine did not differ significantly during the three phases of the study, whereas the methoxyphenamine:5-hydroxymethoxyphenamine and N-desmethylmethoxyphenamine:5-hydroxymethoxyphenamine ratios were significantly altered during the alkaline phase as compared with the other two phases. Therefore, the ratios in terms of O-desmethylmethoxyphenamine are recommended for phenotyping individuals when using methoxyphenamine as a metabolic probe.
在5名健康志愿者身上分三次研究了甲氧苯丙胺（邻甲氧基 - N，α - 二甲基苯乙胺）及其三种代谢产物的处置情况，尿液pH值分别处于未控制、酸性和碱性条件下。所有5名志愿者都是异喹胍和甲氧苯丙胺的广泛代谢者，后者涉及O - 去甲基化和芳香族5 - 羟基化。在研究的三个阶段中，甲氧苯丙胺的血浆峰浓度和0至无穷大的曲线下面积没有显著差异。然而，与碱性尿液条件相比，在酸性尿液条件下，其肾脏清除率平均增加了五倍，血浆终末半衰期缩短了两倍。与碱性尿液条件相比，在未控制pH值和酸性尿液条件下，甲氧苯丙胺及其代谢产物N - 去甲基甲氧苯丙胺和O - 去甲基甲氧苯丙胺的尿排泄量显著增加。相比之下，5 - 羟基甲氧苯丙胺代谢产物的尿排泄不受尿液pH值变化的显著影响。在研究的三个阶段中，甲氧苯丙胺：O - 去甲基甲氧苯丙胺和N - 去甲基甲氧苯丙胺：O - 去甲基甲氧苯丙胺的平均尿排泄率没有显著差异，而与其他两个阶段相比，在碱性阶段甲氧苯丙胺：5 - 羟基甲氧苯丙胺和N - 去甲基甲氧苯丙胺：5 - 羟基甲氧苯丙胺的比率发生了显著变化。因此，当使用甲氧苯丙胺作为代谢探针时，建议用O - 去甲基甲氧苯丙胺的比率来对个体进行表型分析。
