What is the elimination time for nortriptyline (tricyclic antidepressant) in a typical adult patient with normal renal and hepatic function?

Nortriptyline Elimination Time

The elimination half-life of nortriptyline in adults with normal renal and hepatic function ranges from 14 to 51 hours, with most patients experiencing approximately 30-36 hours, and complete elimination requiring approximately 5-7 days (5 half-lives). 1

Pharmacokinetic Parameters

• The typical elimination half-life is 18-28 hours according to general TCA pharmacokinetic data, though individual variation is substantial 2
• Steady-state plasma concentrations are achieved within approximately 5-7 days of consistent dosing, representing approximately 5 half-lives 1
• Complete drug elimination requires at least 5 half-lives, translating to a washout period of approximately 7 days for practical clinical purposes 3

Clinical Context for Elimination Time

• For medication discontinuation or switching, allow a minimum of 1 week (7 days) for complete washout to account for individual pharmacokinetic variability and the presence of active metabolites 3
• Therapeutic drug monitoring should occur at steady state (approximately 1 week after stable dosing) with samples collected 12-16 hours after the last dose 1
• The narrow therapeutic window (50-150 ng/mL) makes understanding elimination kinetics particularly important for both efficacy and safety 1

Important Caveats and Special Populations

Normal Renal Function

• Nortriptyline elimination itself is unaltered in chronic renal failure, as the parent drug undergoes hepatic metabolism 4, 5
• Metabolite elimination (10-hydroxynortriptyline) is significantly reduced in renal impairment, though this does not affect parent drug clearance 4
• The median half-life in renal failure patients (25.2 hours, range 14.5-140 hours) is similar to normal populations 5

Hepatic Function

• Hepatic insufficiency significantly affects elimination since nortriptyline undergoes extensive hepatic metabolism 3
• Patients with hepatic impairment may require 10-14 days for complete washout rather than the standard 7 days 3

Massive Overdose Situations

• At toxic ingestion levels, routine pharmacokinetics become unreliable due to delayed absorption, enterohepatic recirculation, large volume of distribution, and saturable kinetics 6
• One case report documented an elimination half-life of 184 hours (7.7 days) following massive overdose, compared to the typical 14-51 hours 6
• In overdose management, pharmacokinetic values derived from routine dosing should not guide clinical decisions; instead, use QRS duration and urine TCA screens 6

Genetic Polymorphisms

• CYP2D6 poor metabolizers may have substantially prolonged elimination and require extended washout periods 3
• Genetic polymorphisms in CYP2D6 and CYP2C19 can significantly affect TCA metabolism, with poor metabolizers (5-8% of Caucasians) at higher risk of adverse effects 2
• Consider therapeutic drug monitoring or genotyping when timing of medication changes is critical 3

Dose-Dependent Kinetics

• Capacity-limited metabolism can occur at therapeutic doses in some patients, resulting in disproportionately increased plasma concentrations and prolonged half-lives (up to 64 hours documented) 7
• This saturation phenomenon means that doubling the dose may more than double the plasma concentration 8, 7

Practical Clinical Algorithm

For standard discontinuation or medication switching:

1. Allow 7 days minimum for complete washout in patients with normal hepatic function 3
2. Extend to 10-14 days in patients with hepatic impairment 3
3. Consider therapeutic drug monitoring if rapid medication changes are needed 3

For patients with unknown CYP2D6 status and concerning symptoms:

1. Consider genotyping or therapeutic drug monitoring 3
2. Extend washout period if patient is taking CYP2D6 inhibitors 3