Amitriptyline
Amitriptyline. Tertiary-amine TCA — strong serotonin + norepinephrine reuptake inhibition + H1 + muscarinic + α1 antagonism. Now used mainly… Oral half-life 16 h.
Tertiary-amine TCA — strong serotonin + norepinephrine reuptake inhibition + H1 + muscarinic + α1 antagonism. Now used mainly off-label for chronic pain, migraine prophylaxis, neuropathic pain at low doses (10–50 mg). High anticholinergic burden in elderly.
PK re-sourced to Schulz 1983 (PMID:6825390), 7 young and 5 elderly healthy men given a parenteral or oral dose — verbatim "Mean t 1/2 was longer in the older (21.7 +/- 2.9 hr) than in the younger group (16.2 +/- 6.1 hr) as a result of an increase in the volume of distribution (17.1 +/- 2.4 and 14.1 +/- 2.0 l/kg)". The young-adult figures are stored: 16.2 h and 14.1 L/kg (987 L at 70 kg). Because that study has a parenteral arm the volume is ABSOLUTE, not apparent. The stored 21 h silently encoded the ELDERLY value as the general one, and the stored 1100 L fell between the two groups without matching either. ka 1.5 /h and F 0.5 dropped: the previous citation states neither, and its numbers (17, 61.5, 18.8, 30.6) are clearances in L/h, a digit-collision trap.
Pharmacokinetics
- Oral — t½ 16.2 h · Vd 987 L
Sources: PMID:711927, PMID:6825390