Pharmacokinetics of reboxetine in elderly patients with depressive disorders.
OBJECTIVE
To examine the pharmacokinetic characteristics of the selective norepinephrine reuptake inhibitor, reboxetine, in elderly patients with depression.


METHODS
Twelve female inpatients (mean age 80 +/- 4 years) with major depressive or dysthymic disorder were enrolled in a 4-week uncontrolled study of oral reboxetine 2-8 mg/day.


METHODS
After a one-week washout period, patients were randomized into two groups (groups A and B, n = 6/group). Reboxetine was given twice daily, starting with 2 mg/day during week 1 and increasing by 2 mg/day each week to 8 mg/day in week 4. Pharmacokinetic evaluations were carried out at two dosage levels in each group: at the end of weeks 1 and 3 in group A (2 and 6 mg/day), and at the end of weeks 2 and 4 in group B (4 and 8 mg/day). Blood and urine samples were taken for determination of reboxetine pharmacokinetics.


RESULTS
Reboxetine displayed linear pharmacokinetics, with dose-proportional changes, in elderly depressed patients. Mean total urinary recovery ranged from 4.06 to 6.17%. The mean area under the plasma concentration-time curve (AUCtau) and the maximum plasma drug concentration (Cmax) showed considerable variation between patients; at a dosage of 4 mg/day, AUCtau was 1,466-6,866 ngxh/ml and Cmax ranged from 169 to 663 ng/ml.


CONCLUSIONS
The pharmacokinetics of reboxetine are linear across the dosage range of 2-8 mg/day in elderly depressed patients, although Cmax and AUCtau values are higher (and more variable) than in young adults. These results support the use of a lower starting dose (4 mg/day) of reboxetine in the elderly.
Poggesi
I
I
Pharmacokinetics and Metabolism Department, Pharmacia and Upjohn S.p.A., Milano, Italy.
Pellizzoni
C
C
Fleishaker
J C
JC
D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D003866:Depressive Disorder / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D009025:Morpholines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000077593:Reboxetine
D018759:Adrenergic Uptake Inhibitors; D009025:Morpholines; D000077593:Reboxetine