Bellward G D, Warren P M, Howald W, Axelson J E, Abbott F S
Clin Pharmacol Ther. 1977 Jul;22(1):92-9. doi: 10.1002/cpt197722192.
The subjects were 12 male patients stabilized on methadone for many months or years. A comparison was made of the plasma levels and renal clearance of methadone between patients on "high" doses (80 to 110 mg/day) and those on "low" doses (15 to 40 mg/day). A general trend to higher renal clearance was seen in the "high" -dose group, but on more detailed examination there was a direct correlation only when the patients were categorized by urinary pH. At low pHs, there was nearly a 3-fold increase in renal clearance which was associated with a decreased major metabolite to methadone ratio. No evidence for a difference in rate of metabolism between the two groups was found nor were there differences in hepatic function. It was concluded that urinary pH was a major factor in renal clearance of methadone.
研究对象为12名服用美沙酮已达数月或数年且病情稳定的男性患者。对“高”剂量组（80至110毫克/天）和美沙酮“低”剂量组（15至40毫克/天）患者的血浆美沙酮水平及肾脏清除率进行了比较。“高”剂量组呈现出肾脏清除率较高的总体趋势，但经过更详细的检查发现，只有当患者按照尿液pH值进行分类时，二者才存在直接关联。在低pH值情况下，肾脏清除率几乎增加了3倍，这与主要代谢产物与美沙酮的比例降低有关。未发现两组之间代谢速率存在差异，肝功能也无差异。研究得出结论，尿液pH值是美沙酮肾脏清除率的主要影响因素。
