Amitriptyline blood level

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. 

Thus, the patient with a toxic TCA concentration (see the case at the start of the Metabolism section) developed excessively high amitriptyline plasma levels due to the additive effects of diminished left ventricular function leading to decreased hepatic arterial blood flow alcohol and age-related decline in liver function and, finally. 

Mitchell and Groat (526), by contrast, found active drug therapy only marginally effective in the treatment of bulimia nervosa. This may have been due in part to the relatively low amitriptyline doses used (maximum 150 mg per day), resulting in average blood levels of only 103 ng/mL. 

Much of the study of interethnic differences in the pharmacokinetics and pharmacodynamics of psychotropic medications has involved TCAs and differences between Asians and Caucasians (Pi et al. 1993a). As with antipsychotics, there are clinical reports that Asians require lower doses of TCAs (Pi and Gray 1998 Pi et al. 1993a). It has also been suggested that Asians show a therapeutic response at lower blood levels of TCAs (Yamashita and Asano 1979), suggesting pharmacodynamic differences. Other studies of prescribing patterns have failed to confirm this and found that the daily doses of amitriptyline, imipramine, doxepin, and nortriptyline prescribed by psychiatrists at 29 medical schools in 9 Asian countries were the same as those used in the United States (Pi et al. 1985). It was also reported that Asians and whites need similar doses of at least 150 mg/day to attain recommended therapeutic blood concentrations (Kinzie et al. 1987). 

Demorest DM. Distinguishing cyclobenzaprine from amitriptyline and imipramine by liquid chromatography with UV multi-wavelength or full-spectrum detection. Blood levels of cyclobenzaprine in emergency screens. J Anal Toxicol 1987 11 133 (Letter). 

A meta-analysis of the TCA blood level literature using ROC curves as the primary statistical tool determined the recommended therapeutic thresholds or ranges for four TCAs nortriptyline, desipramine, amitriptyline, and imi-pramine. A summary of these data are presented in Table 9.5. 

Corona CL, Cucchi ML, Santagostino G, et al Blood noradrenahne and 5-HT levels in depressed women during amitriptyline or lithium treatment. Psychopharmacology 77 236-241, 1982... 

TCAs ANTIDIABETIC DRUGS Likely to impair control of diabetes. TCAs may t serum glucose levels by up to 150%, t appetite (particularly carbohydrate craving) and i metabolic rate Be aware and monitor blood sugar weekly until stable. Generally considered safe unless diabetes is poorly controlled or is associated with significant cardiac or renal disease. Amitriptyline, imipramine and citalopram are also used to treat painful diabetic neuropathy... 

St John s wort 1. TCAs (e.g. amitrypty-line, nortryptiline, clomipramine) 2. SSRIs (e.g. fluvoxamine, fluoxetine) 3. Venlafaxine Low blood amitriptyline levels (<20%). May potentially 1 therapeutic effects. Nortriptyline levels may be i by 50%. St John s wort t sedative effects (weakness, lethargy, fatigue, slow movements, incoherence) of SSRIs Due to induction of metabolizing CYP3A4 enzyme and P-gp transport proteins St John s wort inhibits uptake of serotonin and thereby t serotonin levels Avoid concomitant use... 

Very few fatalities have ever been reported (or studied), but it appears that the therapeutic index for ephedrine is very great. A 1997 case report described a 28-year-old woman with two prior suicide attempts, who died after ingesting amitriptyline and ephedrine. The blood ephedrine concentration was 11,000 ng/mL, and the liver concentration was twice that value (kidney, 14 mg/kg brain, 8.9 mg/kg). The amitriptyline concentration was 0.33 mg/kg in blood and 7.8 mg/kg in liver (131). Values in a second case report (where methylephedrine concentrations were nearly 6000 ng/mL) may or may not be relevant to the problem of ephedrine toxicity, as the individual in question took massive quantities of a calcium channel blocker, and it is not known whether methylephedrine exerts all the same effects as ephedrine (132). Baselt and Cravey mention the case of a young woman who died several hours after ingesting 2.1 g of ephedrine combined with 7.0 g of caffeine, but tissue findings were not described. Her blood ephedrine level was 5 mg/L, whereas the concentration in the liver was 15 mg/kg (133). 

HT turnover. Others 28 have shown that chlorimipramine lowers CSF 5-HIAA in depressed patients, and it was reported29 that chlorimipramine, amitriptyline, and desipramine all reduce blood tryptophan levels. Earlier it had been mentioned that chlorimipramine lowered whole blood 5-HT. 18 It has also been shown that chlorimipramine and tryptophan were better in treating depression than chlorimipramine alone,28 however elsewhere 20 it was reported that no significant difference between any of the following treatment modalities was found chlorimipramine, chlorimipramine plus... 

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