Nortriptyline and 10-hydroxynortriptyline plasma concentrations
Ziegler, V.E.; Fuller, T.A.; Biggs, J.T.
Journal of Pharmacy and Pharmacology 28(11): 849-850
1976
ISSN/ISBN: 0022-3573 PMID: 11300 Document Number: 104525
To examine the relation between nortriptyline concentrations and therapeutic response and side-effects, the amount of 10-hydroxynortriptyline in patients' plasma was quantitated. In 36 patients the mean total plasma 10-hydroxynortriptyline concentration was 3.64 times greater than that for nortriptyline; the much smaller ratio (0.80) of free 10-hydroxynortriptyline: nortriptyline makes it unlikely that 10-hydroxynortriptyline plays a significant biological role in patients undergoing treatment with nortriptyline unless the 10-hydroxy compound is more potent. Animal studies and multiple studies on human urine suggested that hydroxylation is a factor controlling individual differences in plasma steady-state concentrations. Hydroxylation is probably the major determinant of plasma steady-state nortriptyline concentrations, even when factors such as individual differences in wt, body mass and other routes of degradation are not considered.