Plasma Levels Of Nortriptyline Research Articles

Correlation of subjective side effects with plasma concentrations of nortriptyline.

Plasma levels of tricyclic antidepressant drugs vary considerably between individuals receiving the same amount of drug. The bearing of this variation on the occurrence of subjective side effects was investigated in 40 psychiatric inpatients with depressive disorders. Plasma levels were determined before and during four weeks of treatment with nortriptyline 50 mg. three times a day and patients were rated for subjective side effects, the assessors being unaware of the plasma levels of the drug.Plasma levels varied widely between individual patients, but in any given patient the plasma level tended to be constant over a period of time. The side effects of nortriptyline diminished significantly with time and were in most cases absent during the fourth week of treatment. There was a significant positive correlation between plasma level of nortriptyline and subjective side effects.The steady-state plasma level of a drug which is metabolized is usually a more important determinant for its effect than dosage, since it reflects the amount of drug available for biological action. Very high plasma levels of nortriptyline should presumably be avoided, since there is no evidence that they are needed for therapeutic effect and they are potentially harmful.

The role of plasma protein binding in the inhibitory effect of nortriptyline on the neuronal uptake of norepinephrine.

The inhibitory effect of nortriptyline (NT) on the neuronal uptake of radio labeled norepinephrine (NE) was studied with the use of the rat iris preparation in Krebs‐Ringer solution or human plasma. When added to the incubation medium, NT inhibited the uptake of NE approximately ten times as effectively in buffer as in human plasma within the tested concentration range of NT (10−8 to 10−6M). This result is in good agreement with the 94 per cent binding (at NT concentration of 1.1 10−6M) obtained by the ultrafiltration method. Plasma from patients treated with NT also inhibited the uptake of NE. Correlation between the inhibitory effect and the “endogenous” plasma level of NT in the 14 patients studied was significant (p < 0.001). When NT was added in different concentrations to control plasma the inhibitory effect observed was close to that obtained with patient plasma containing the same “endogenous” concentration of NT.

Tyramine pressor effects in man before and during treatment with nortriptyline or ECT: Correlation between plasma level and effect of nortriptyline

Systolic pressor effects after i.v. injection of tyramine (TA) were recorded in 13 patients before and during treatment with nortriptyline (NT) in doses of 1.4–5 mg/kg/day for 3–4 weeks. After NT a several fold decrease in the responsiveness to TA occurred. Patients given the same dose of NT showed markedly different decreases in the responsiveness to TA. There was no correlation between the blockade of the TA pressor effects and the dose of NT employed but there was an excellent correlation between the blockade and the plasma level of NT (p<0.001 and p<0.005 respectively). TA pressor effects were not changed in a small control group of depressed patients after treatment with E.C.T. The relationship between kinetics and effects of tricyclic antidepressants is discussed. The steady-state plasma level of NT seems to be an important determinant of its effects.

Circulatory effects in man of nortriptyline, a tricyclic antidepressant drug

In 40 depressed patients treated with 25 or 50 mg nortriptyline (NT) t. i. d. for 3 weeks the following circulatory variables were observed prior to and during drug therapy: heart rate and blood pressure at rest (in supine and standing positions), working capacity, ECG at rest and during exercise on a bicycle ergometer. During administration of NT the heart rate increased significantly at rest in both supine and standing positions, but the orthostatic heart rate reaction remained unchanged. Diastolic blood pressure in the supine position rose slightly; in the standing position the pretreatment increase in diastolic pressure was abolished. The positive chronotropic effect did not correlate with the steady-state plasma level of NT. In one patient on NT a right bundle branch block appeared during the work test; in the remaining 39 patients the ECG records at rest and during exercise showed no adverse effects of NT.

Steady-state plasma levels of nortriptyline in twins: influence of genetic factors and drug therapy.

Nineteen identical (monozygotic) and 20 fraternal (dizygotic) sets of twins between 45 and 51 years of age were given nortriptyline orally in doses of 0.2 mg./kg. body weight three times daily for eight days. The steady-state plasma concentrations of nortriptyline were calculated from the mean of the determinations for days 6, 7, and 8. Identical twins, not treated with other drugs, achieved similar steady-state plasma concentrations of nortriptyline in contrast to fraternal twins who were not given other drugs. The intrapair similarity in steady-state plasma concentrations was not found in identical twins simultaneously treated with various drugs during the experiment. Identical and fraternal twins treated with drugs containing barbiturates had considerably lower steady-state plasma concentrations of nortriptyline compared with untreated twins.It is concluded that most of the variability in nor-triptyline steady-state plasma concentration between persons who have not received drugs is genetically determined. Exposure to other drugs also influences the steady-state plasma concentration of nortriptyline, which in a given patient may therefore be determined by a resultant of genetic and environmental factors.