Amitriptyline and nortriptyline

Note Derivatization with this reagent sequence in combination with extraction and TLC separation is speciftc for amitriptyline and nortriptyline in the analysis of plasma furthermore its high sensitivity allows its employment in pharmacokinetic studies, e. g. after the oral administration of a single dose of 25 mg amitriptyline. 

The amino derivatives of amitriptyline and nortriptyline produced at the second heating stage exhibit intense pale yellow fluorescence on examination in long-wavelength UV light (X,= 365 nm), but this is not sufficiently reproducible for quantitative in situ work. 

The detection limits for amitriptyline and nortriptyline are ca. 500 pg substance per chromatogram zone. 

T. Heikkinen, U. Ekblad, and K. Laine. Transplacental transfer of amitriptyline and nortriptyline in isolated perfused human placenta. Psychopharmacology (Berl). 153 450-454 (2001). 

Several drugs sharing a number of chemical features and therapeutic properties are included in this category. The most widely used at the present time are imipramine, desipramine, amitriptyline, and nortriptyline. Not all authors have distinguished clearly between them, and some have uncritically equated results obtained with two different drugs as though they were identical (B34). 

Braithwaite et al. (B20) treated fifteen patients with a fixed daily dose of 150 mg of amitriptyline by mouth for 6 weeks. Plasma amitriptyline and nortriptyline levels were measured, by GLC, in venous blood collected 19 hours ( SD 4.3 hours) after the last dose of the drug. Steady-state blood levels were achieved within 2 weeks, on average, but there were large between patient differences. 

The ratio between amitriptyline and nortriptyline levels at equilibrium also varied widely. Good clinical response to the drug after 6 weeks treatment, correlated with the presence of a total plasma tricyclic... 

B19. Braithwaite, R. A., and Widdop, B., A specific gas chromatographic method for measurement of steady state plasma levels of amitriptyline and nortriptyline in patients. Clin. Chim. Acta 35, 461-473 (1971). 

Jerling, M., Bertilsson, L., and Sjoqvist, F. (1994) The use of therapeutic drug monitoring data to document kinetic drug interactions an example with amitriptyline and nortriptyline. Ther Drug Monit 16 1-12. 

Maprotiline and bupropion cause more seizures than agents such as imipramine, amitriptyline, and nortriptyline. This issue, plus other safety concerns, has significantly limited the use of maprotiline. If maprotiline is used, many clinicians start with a low dose (75 mg per day or less in elderly patients), gradually increasing by 25-mg increments over 2 or more weeks (the drug has a half-life of about 48 hours). Average doses in outpatients are 150 mg, with a maximum of 225 mg. 

Tricyclic antidepressants. Imipramine and clomipramine have been the most extensively studied of the tricyclic antidepressants and both have demonstrated efficacy in treating panic disorder. Other tricyclic antidepressants that have shown some evidence of efficacy include desipramine, doxepin, amitriptyline, and nortriptyline. 

In the past, tricyclic drugs such as amitriptyline and nortriptyline were the most commonly used antidepressants and were the standard against which other antidepressants were measured.30 The use of tricyclic drugs as the initial treatment of depression has diminished somewhat in favor of some of the newer second-generation drugs, which may have more favorable side-effect profiles. Tricyclic agents, nonetheless, remain an important component in the management of depressive disorders, especially in more severe forms of depression that fail to respond to other antidepressants.6,53... 

Hence, there is little doubt that antidepressants may be useful as an adjunct in the treatment of patients with chronic pain. Traditional tricyclic medications such as amitriptyline and nortriptyline are often considered the drugs of choice for chronic pain.52 Newer drugs such as the SSRIs (e.g., paroxetine) and SNRIs (e.g., venlafaxine) might also be considered for some patients with fibromyalgia, neuropathies, and other forms of chronic pain.29 Future research should help clarify how specific antidepressants can be used most effectively as part of a comprehensive regimen for treating various types of chronic pain. 

TCAs VALPROATE t amitriptyline and nortriptyline levels Uncertain Be aware watch for clinical features of t levels of these TCAs (e.g. sedation, dry mouth)... 

Quantification. Gas Chromatography. In plasma amitriptyline and nortriptyline, detection limit lOng/ml, AFID—S. Dawling and R. A. Braithwaite, J. Chromat., 1978,146 Biomed. Appl, 3,449-456. 

High Pressure Liquid Chromatography. In plasma amitriptyline and nortriptyline, UV detection—B. Mellstrom and R. Braithwaite, J. Chromat., 1978, 157, 379-385. In plasma or serum amitriptyline and nortriptyline, sensitivity 5 ng/ml, UV detection—P. M. Kabra et al., Clinica chim. Acta, 1981, 111, 123-132. In urine amitriptyline and major metabolites, detection limit 100 ng/ml, UV detection—S. R. Biggs et al. Drug Met. Disp., 1979, 7, 233-2216. 

Brixen-Rasmussen L, Halgrener J, j0rgensen A. Amitriptyline and nortriptyline excretion in human breast milk. Psychopharmacology 1982 76 94—5. 

Tricyclic antidepressants. Imipramine, amitriptyline and nortriptyline are effective, especially for nocturnal but also for daytime incontinence. Their parasympathetic blocking (antimuscarinic) action is probably in part responsible but imipramine... 

In 10 patients taking amitriptyline 125 mg/day, for 20 days valpromide increased amitriptyline and nortriptyline plasma concentrations from 71 to 106 ng/ml for amitriptyline, and from 61 to 101 ng/ml for nortriptyline (142). 

Bertschy G, Vandel S, Jounet JM, Allers G. Interaction valpromide-amitriptyline. Augmentation de la biodisponi-bilite de 1 amitriptyline et de la nortriptyline par le valpro-mide. [Valpromide-amitriptyline interaction. Increase in the bioavailability of amitriptyline and nortriptyline caused by valpromide.] Encephale 1990 16(l) 43-5... 

Wong ECC, Koenig J, Turk J. Potential interference of cyclobenzaprine and norcyclobenzaprine with HPLC measurement of amitriptyline and nortriptyline Resolution by GC-MS analysis. J Anal Toxicol 1995 19 218-24. 

Steimer W, Zopf K, Von Amelunxen S, Pfeiffer H, Bachofer J, Popp J, et al. Allele-specific change of concentration and functional gene dose for the prediction of steady-state serum concentrations of amitriptyline and nortriptyline in CYP2C19 and CYP2D6 extensive and intermediate metabolizers. Clin Chem 2004 50 1623-33. 

GP Mould, G Stout, GW Aherne, V Marks. Radioimmunoassay of amitriptyline and nortriptyline in body fluids. Ann Clin Biochem 15 221, 1978. 

R Lucek, R Dixon. Specific radioimmunoassay for amitriptyline and nortriptyline in plasma. Res Commun Chem Pathol Pharmacol 18 125, 1977. 

Clinically, protriptyline is a purer type of antidepressant agent, in that it lacks the sedative properties of amitriptyline and nortriptyline. It is said to be the more potent of the three agents and useful also in the treatment of anxiety depressions. However, until further clinical work is published, it will be difficult to assess the therapeutic spectrum of this most recent agent. 

Svensson, C. Nyberg, G. MSrtensson, E. High-performance liquid chromatographic quantitation of amitriptyline and nortriptyline in dialysate from plasma or serum using on-line solid-phase extraction. 

Terlinden, R. Borbe, H.O. Determination of amitriptylinoxide and its major metabolites amitriptyline and nortriptyline in plasma by high-performance liquid chromatography. J.Chromatogr., 1986, 382, 372-376 [plasma column temp 45 extracted amitriptylinoxide desipramine (IS) LOQ 10 ng/mL pharmacokinetics dog]... 

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