Age and nortriptyline concentrations in plasma ultrafiltrate

Objectives. Since plasma protein binding of tricyclic antidepressants may b e relevant to treatment effects and can be influenced by age-associated fac tors, we examined both plasma ultrafiltrate and total concentrations of nor triptyline (NT) in patients and compared these to age. We hypothesized nega tive associations with age of both ultrafiltrate NT and the ratio of ultraf iltrate NT to total plasma NT. Methods. Patients with major depression at a psychiatric service treated wi th a stable dose of NT were studied. Trough plasma ultrafilrate NT concentr ations 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 concentrat ions were both significantly negatively associated with age. Total NT conce ntrations were not significantly associated with age. Conclusions. Relatively low ultrafiltrate NT concentrations in older patien ts may reflect lower tissue exposure at a given total plasma NT concentrati on. This could be relevant to toxic and therapeutic effects. Studies of rel ationships between non-bound drug concentrations and NT treatment outcomes across the age span are needed. Copyright (C) 2000 John Wiley & Sons, Ltd.