The effect of age on the plasma levels of amoxapine and its major metabolite in depressed patients

Twenty-eight depressed patients receiving amoxapine with ages ranging from 21 to 68 years (male 12, female 16) were studied in order to clarify the age effect on plasma levels of amoxapine and its major active metabolite, 8-OH amoxapine. Plasma amoxapine levels were determined by both radioreceptor assay (RRA) and gas liquid chromatography (GLC). Plasma levels of 8-OH amoxapine were also determined by GLC. A highly significant correlation was found for plasma levels of amoxapine determined by RRA and GLC (r = 0.88, p < 0.001). There was no significant correlation between the amoxapine daily dose (mg/kg) and its plasma levels determined either by RRA or GLC. The ratios of plasma amoxapine level by RRA and GLC to daily dose significantly increased with advancing age (p < 0.05) and a significant positive correlation was also found between the ratio of plasma level of 8–OH amoxapine to daily dose and the age of the patients (p < 0.01), suggesting that the plasma 8-OH amoxapine levels were more strongly affected by age than the parent drug. These results indicate that the metabolism of amoxapine in the liver decreases with age as well as that of other tricyclic antidepressants reported previously. The higher correlation of 8-OH amoxapine with patient's age may be mainly due to its renal excretion which may also decrease with age.