The pharmacokinetics of nortriptyline in patients with chronic renal failure.

Abstract

1 The pharmacokinetics of single oral doses of nortriptyline were studied in twenty patients with chronic renal failure, eight of whom were receiving treatment with haemodialysis. 2 The median nortriptyline half‐life was 25.2 h (range 14.5‐140.0 h) and the median nortriptyline clearance was 32.3 l/h (range 8.1‐122.0 l/h). 3 No differences were observed between the dialysed and non‐dialysed groups. 4 Comparisons of nortriptyline half‐life and clearance between the patients and groups of physically healthy subjects revealed no significant differences. 5 There was no significant linear correlation between age and either of these measurements. In the twelve patients not receiving haemodialysis there was no correlation between nortriptyline clearance and glomerular filtration rate. 6 Chronic renal failure is not associated with a significant alteration in nortriptyline metabolism as measured by its half‐life or clearance, but the drug should nonetheless be used with caution, and monitored whenever possible. However, the marked inter‐ individual differences observed in nortriptyline half‐life and clearance in patients with chronic renal failure may not be solely responsible for their unpredictable response to tricyclic antidepressant therapy, and other possible contributory factors are discussed.

Pharmacokinetics of antidepressants in patients undergoing hemodialysis: a narrative literature review

“…We found one study regarding pharmacokinetics of tianeptine,18 one on citalopram,19 one on fluvoxamine,20 one on sertraline, 21 one on nefazodone, 22 one on nortriptyline, 23 one on amitriptyline, 24 three on mirtazapine,24-26 and two on fluoxetine27,28 in patients undergoing hemodialysis. Our findings are described below.…”

Extracorporeal Treatment for Tricyclic Antidepressant Poisoning: Recommendations from the EXTRIP Workgroup

“…From the initial 1312 studies obtained, 77 studies met the inclusion criteria, including 1 observational study , 5 animal studies , 4 in vitro studies , 4 pharmacokinetic (PK) studies , and 63 case reports , 39 of which had sufficient toxicokinetic (TK) data. In total, 108 patients were included for analysis.…”

“…Pharmacokinetic studies of TCA removal in nonpoisoned end‐stage renal disease (ESRD) patients reveal similar results: in two studies, HD did not alter TCA kinetics . In another prospective study of five ESRD patients, a single HD session removed on average 37 μ g in 4 hours, which was <1% of the administered oral dose of doxepin .…”

Psychotherapeutic Agents in End‐Stage Renal Disease

“…Tricyclic antidepressants have been used successfully in patients with ESRD to treat depression, and in the case of doxepin, uremic pruritis. Amitriptyline and its active metabolite nortriptyline have similar half‐lives compared to healthy volunteers, although inter‐ and intra‐individual variability in concentrations has been reported to be high . The conjugated metabolites of the TCAs have the potential to accumulate in patients with ESRD.…”