Relationship of hydroxynortriptyline to nortriptyline concentration and creatinine clearance in depressed elderly...

Plasma concentration of E-10-hydroxynortriptyline is increased in the elderly and may be related to both renal clearance of hydroxynortriptyline and rate of liver hydroxylation of nortriptyline. In 25 ambulatory, depressed elderly outpatients treated with therapeutic doses of nortriptyline, relationships among plasma levels of nortriptyline and E-10-hydroxynortriptyline, and an estimate of creatinine clearance were examined. Plasma levels of E-10-hydroxynortriptyline (corrected for varying dosage) were significantly correlated with age and inversely correlated (r = -0.50) with creatinine clearance but not with notriptyline or Z-10-hydroxynortriptyline concentration. E-10-hydroxynortriptyline concentration was about 5 1/2 times that of Z-10-hydroxynortriptyline. By best subsets multiple regression analyses, the ratio of E-10-hydroxynortriptyline to nortriptyline level was best predicted by plasma nortriptyline concentration, creatinine clearance, and age, all of which accounted for 63% of the variance. These results corroborate and extend previous findings in elderly inpatients in whom creatinine clearance was measured directly. In addition, age had an effect on E-10-hydroxynortriptyline independently of creatinine clearance. Since E-10-hydroxynortriptyline concentration has been related to both therapeutic efficacy and toxicity during nortriptyline treatment, it may be important to assess nortriptyline hydroxymetabolites in elderly patients and in those with renal insufficiency.