Nortriptyline
Nortriptyline. Secondary-amine TCA — active metabolite of amitriptyline. Stronger NE reuptake / weaker serotonergic + lower anticholinergic… Oral half-life 39 h.
Secondary-amine TCA — active metabolite of amitriptyline. Stronger NE reuptake / weaker serotonergic + lower anticholinergic burden vs amitriptyline. Better-tolerated TCA for chronic pain, depression-with-pain, smoking cessation.
PK: its source_pmid was a NARRATIVE REVIEW whose abstract contains not one number. V 1500 L has NO SOURCE ANYWHERE in the literature — a plausible textbook figure with nothing behind it — and is dropped. The half-life is corrected to the stated 39 h; the stored 30 h sits at the ADOLESCENT mean rather than the adult one. F 0.55 lies inside a stated "varied from 0.46 to 0.59 in 6 subjects" but is nowhere stated, so the lower endpoint is carried. AN EFFECT COMPARTMENT IS STRUCTURALLY WRONG FOR THIS DRUG AND THE RECORD IS RIGHT TO HAVE NONE: the concentration-effect relation is NON-MONOTONIC — "Amelioration was most pronounced in the intermediate plasma level range (50-139 ng/ml) and was slight both at lower and at higher plasma levels" — and no equilibration constant can represent a curve that falls again at high concentration. The therapeutic window needs an upper bound, not a half-maximal concentration. USEFUL STRUCTURAL FACT: enzyme inhibition changes clearance "whereas the volume of distribution was unchanged", so volume is the robust parameter here and clearance the fragile one. A trap is logged: a 66% figure in this literature is relative to INTRAMUSCULAR dosing and its own authors say so.
Pharmacokinetics
- Oral — t½ 39 h · F 46%
Sources: PMID:7366812, PMID:1164819, PMID:5558186