Age and nortriptyline concentrations in plasma ultrafiltrate.
OBJECTIVE
Since plasma protein binding of tricyclic antidepressants may be relevant to treatment effects and can be influenced by age-associated factors, we examined both plasma ultrafiltrate and total concentrations of nortriptyline (NT) in patients and compared these to age. We hypothesized negative associations with age of both ultrafiltrate NT and the ratio of ultrafiltrate NT to total plasma NT.


METHODS
Patients with major depression at a psychiatric service treated with a stable dose of NT were studied. Trough plasma ultrafiltrate NT concentrations and total plasma NT concentrations were measured by high performance liquid chromatography. Concentrations were corrected for dose.


RESULTS
Eighty-seven patients aged 26 - 88 years were studied. Ultrafiltrate NT concentrations and the ratio of ultrafiltrate NT to total NT concentrations were both significantly negatively associated with age. Total NT concentrations were not significantly associated with age.


CONCLUSIONS
Relatively low ultrafiltrate NT concentrations in older patients may reflect lower tissue exposure at a given total plasma NT concentration. This could be relevant to toxic and therapeutic effects. Studies of relationships between non-bound drug concentrations and NT treatment outcomes across the age span are needed.
Young
R C
RC
The New York Presbyterian Hospital, Westchester Division, White Plains, New York, USA.
Dhar
A K
AK
Hull
J
J
Kakuma
T
T
Alexopoulos
G S
GS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001682:Biological Availability; D003865:Major Depressive Disorder / Q000097:blood* / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006440:Hemofiltration; D006801:Humans; D008297:Male; D008875:Middle Aged; D009661:Nortriptyline / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011485:Protein Binding / Q000502:physiology
D009661:Nortriptyline