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Results for “NORTRIPTYLINE”

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At least 253 records · Page 14Linked to original sources

PubMed1998

High-performance liquid chromatography-mass spectrometry for the quantification of nortriptyline and 10-hydroxynortriptyline in plasma.

A highly sensitive and selective method for the quantification of nortriptyline and its major 10-hydroxy metabolite in plasma is described. The method is based on liquid-liquid extraction in combination with acid dehydration of the 10-hydroxy metabolite to the less polar 10,11-dehydronortriptyline. Deuterium labelled internal standards ([2H4]NT and [2H3]10-OH-NT) were used and the compounds were separated by reversed-phase HPLC and detected using atmospheric pressure chemical ionisation and mass spectrometry. The limit of quantification was 0.8 ng/ml for both compounds. A 1-ml volume of plasma was used for analysis in the concentration range 0.8-32 ng/ml. The within- and between-day coefficients of variation were 11% in the low, 1.6 ng/ml range, and 7% at 8 ng ml/ml. Using this method it was possible to quantify plasma concentrations for 168 h following a single oral dose of 25 mg of nortriptyline with good accuracy and precision.

Chromatography, High Pressure Liquid↗

PubMed1977

Plasma nortriptyline and clinical response--a study using changing plasma levels.

In a 5-week study of 22 depressed patients treated with nortriptyline, significant changes in plasma levels, both elevated and reduced, were deliberately produced in the third and fourth weeks of each patient's treatment. Correlation of plasma nortriptyline levels and changes in the severity of depression, as measured by the Hamilton Depression Scale, showed no significant relationships. The implications of the study are discussed.

Administration, Oral↗

PubMed1999

Optimal sampling times for Bayesian estimation of the pharmacokinetic parameters of nortriptyline during therapeutic drug monitoring.

Sampling times for Bayesian estimation of the pharmacokinetic parameters of an antidepressant drug, nortriptyline, during its therapeutic drug monitoring were optimized. Our attention was focused on designs including a limited number of measurements: one, two, and three sample designs in which sampling times had to be chosen between 0 and 24 hr after the last intake of a test-dose study. The optimization was conducted in four groups of patients defined by their gender and the administration or not of concomitant drugs inhibiting the metabolism of nortriptyline. The Bayesian design criterion was defined as the expected information provided by an experiment. A stochastic approximation algorithm, the Kiefer-Wolfowitz algorithm, was used for the criterion maximization under experimental constraints. Results showed that optimal Bayesian sampling times differ between patients in monotherapy and polytherapy. For one-sample designs the measurements have to be performed either at the lower (0 hr) or at the upper (24 hr) bound of the admissible interval. Replications were often found for 2- and 3-point designs. Other sampling designs can lead to criterion close to the optimum and can therefore be performed without great loss of information. In contrast, we found that several designs lead to low values of the information criterion, which justifies the approach.

Absorption↗

PubMedDate not supplied

The production of amitriptyline from nortriptyline in formaldehyde-containing solutions.

The stability of nortriptyline in aqueous solutions containing various concentrations of formaldehyde was investigated. Amitriptyline, as a reaction product, was determined by gas chromatography/mass spectrometry (GC/MS) in these experiments. Factors that may contribute to this phenomenon, including pH, formaldehyde concentration, and incubation time were evaluated. At 40% (v/v) formaldehyde concentration and pH 4, there was a 68% decrease in nortriptyline concentration along with a concomitant formation of amitriptyline after 24 h. The N-methylated product was responsible for 48% of the total tricyclic drug present. The data also clearly indicate that the formation of amitriptyline is favored at elevated pH.

Amitriptyline↗

PubMedDate not supplied

The use of bone marrow in the study of postmortem redistribution of nortriptyline.

Thirty-two New Zealand Albino rabbits (1.5-2.0 kg) were dosed on a daily basis with 20 mg/kg nortriptyline (NT) prior to feeding for a period of five days. On the fifth day of dosing, the animals were sacrificed approximately 1.5 h after the final dose. A comparison was made of nortriptyline concentrations in the blood and bone marrow at the time of sacrifice, and between bone marrow collected at the time of sacrifice and bone marrow collected at 2, 4, 6, 12, 24, 36, and 48 h after sacrifice. The results indicate that a linear relationship exists between blood and bone marrow NT concentrations, with an average marrow-to-blood ratio of 29.98 +/- 3.91 and a correlation coefficient of 0.956. Additionally, there was no significant difference (p > 0.05) observed between NT concentrations in bone marrow at the time of sacrifice and its concentration up to 24 h after sacrifice. The results indicate that bone marrow may be used to predict blood concentrations of NT up to 24 h after death when a suitable blood sample is not available.

Animals↗

PubMed2000

Evaluation of platelet activation in depressed patients with ischemic heart disease after paroxetine or nortriptyline treatment.

This study investigated the effects of antidepressant treatment on platelet activation in depressed patients with ischemic heart disease (IHD). Plasma levels of platelet alpha-granule release products beta-thromboglobulin (BTG) and platelet factor 4 (PF4) were measured in 17 depressed patients with IHD who were treated in a 6-week, double-blind trial with either paroxetine (10 patients) or nortriptyline (7 patients). Baseline measurements of BTG and PF4 were significantly elevated in both drug treatment groups before the initiation of antidepressant therapy compared with those of healthy control subjects. In the paroxetine group, mean PF4 and BTG levels significantly decreased from these elevated baseline values within 1 week of treatment and remained low at 3- and 6-week measurements. In contrast, the nortriptyline group did not exhibit a significant decrease in PF4 or BTG plasma levels after 1, 3, or 6 weeks of treatment. Therefore, platelet activation in depressed patients with IHD seems to be inhibited by the selective serotonin reuptake inhibitor paroxetine. The effect of paroxetine on PF4 and BTG plasma levels suggests that it may reduce platelet aggregation in vivo and may positively impact IHD-related mortality in this population.

Antidepressive Agents, Second-Generation↗

PubMed2003

Initial platelet serotonin (5-HT) transport kinetics predict nortriptyline treatment outcome.

According to the hypothesis of initial conditions, drug response may be determined by different initial states of neurotransmitter protein recognition systems. Platelet serotonin (5-HT) transport kinetics were studied as initial-conditions predictors of antidepressant response in 24 depressed patients before and after 3 weeks of treatment with nortriptyline (75 mg). The initial affinity of the 5-HT transporter (5-HTT) correctly predicted 71% of the outcome. The pretreatment affinity constant ( Km) correlated (r = 0.61; p < 0.002) with that measured after 3 weeks of treatment (Kapp). Responding patients had a significantly higher initial Km before treatment and a significantly higher Kapp after treatment. Nonresponders had an initial Km significantly lower than that of 24 controls. Nortriptyline plasma levels were not statistically different between response groups. These results are consistent with two previously published observations, which indicate that the initial affinity of the 5-HTT predicted response to fluvoxamine or fluoxetine in the same way. Insofar as all three drugs increase the apparent affinity of the 5-HTT, it appears that a better response is related to those cases where the initial affinity is already higher before treatment.

Adult↗

PubMed1979

An improved gas-liquid chromatographic procedure for the determination of amitriptyline and nortriptyline levels in plasma using nitrogen-sensitive detectors.

An improved gas-liquid chromatographic procedure for the plasma level determination of amitriptyline and nortriptyline using nitrogen-sensitive detectors is described. Derivatization of the secondary amines using trifluoroacetic anhydride greatly improves the response and reproducibility of the assay. Plasma samples containing as little as 5 ng/ml of amitriptyline and nortriptyline can be assayed precisely and reproducibly, using protriptyline as internal reference standard.

Amitriptyline↗

PubMed1988

Alprazolam does not inhibit the metabolism of nortriptyline in depressed patients or inhibit the metabolism of desipramine in human liver microsomes.

In 10 patients treated with nortriptyline, the steady-state plasma concentrations of the parent drug and the active 10-hydroxy metabolite were very similar before and during concomitant treatment with alprazolam (0.5 mg orally t.i.d.). In human liver microsomes the 2-hydroxylation of desipramine was not inhibited by alprazolam. The absence of an inhibition by alprazolam on the hydroxylations of nortriptyline in vivo and of desipramine in vitro indicates that alprazolam is not metabolized by the debrisoquine hydroxylase.

Adult↗

PubMed1989

Evaluation of the EMIT amitriptyline and nortriptyline assays for the determination of serum clomipramine and desmethylclomipramine.

Homogeneous enzyme immunoassay reagents (EMIT) developed for the measurement of amitriptyline and nortriptyline in serum were modified to allow quantitation of clomipramine and desmethylclomipramine. The method was compared to a high-performance liquid chromatographic method. Between-run precision [coefficient of variation (CV)] for clomipramine in the EMIT assay for amitriptyline ranged from 2.6 to 3.2%. For desmethylclomipramine in the nortriptyline assay, the between-run CV ranged from 1.4 to 1.9%. Serum specimens from 43 patients (desmethylclomipramine) and 59 patients (clomipramine) were analyzed by both methods, with good correlation between methods. For clomipramine, recovery ranged from 100 to 102% (0-600 ng/ml range) and was 95-103% for desmethylclomipramine (0-600 ng/ml). The modified EMIT assays offered sufficient reproducibility, accuracy, and correlation with an established method for routine analysis of clomipramine and desmethylclomipramine.

Amitriptyline↗

PubMed1985

Plasma concentrations of nortriptyline and its 10-hydroxy metabolite in depressed patients--relationship to the debrisoquine hydroxylation metabolic ratio.

In 20 depressed patients treated with nortriptyline (NT) there was a significant relationship between the plasma concentration of NT and the debrisoquine metabolic ratio (rs = 0.77; P less than 0.01). (The debrisoquine test was performed after stopping NT treatment). This is in agreement with the hypothesis that the hydroxylations of NT and debrisoquine are mediated by similar enzymatic mechanisms. In contrast there was no significant relationship between the debrisoquine metabolic ratio and the plasma concentrations of the active metabolite 10-hydroxy-nortriptyline. In 11 of the patients the debrisoquine metabolic ratio was significantly higher during than after NT treatment. This may be due to an inhibition of the debrisoquine hydroxylation by NT.

Debrisoquin↗

PubMed1980

Anti-depressive treatment in Parkinson's disease. A controlled trial of the effect of nortriptyline in patients with Parkinson's disease treated with L-DOPA.

Nineteen patients with L-DOPA treated parkinsonism involving depressive symptoms, the therapeutic effect of nortriptyline was compared to placebo in a controlled trial. The depressive and neurological symptoms were evaluated by rating scales. Nortriptyline had a clinical significant effect with regard to the depressive symptoms, whereas the neurological parameters were unchanged. The authors suggest the depression in Parkinson's disease to be of both reactive and endogenous origins.

Aged↗

PubMed1978

A clinical trial comparing sustained release amitryptyline (Saroten Retard) and conventional amitriptyline tablets (Saroten) in endogenously depressed patients with simultaneous determination of serum levels of amitryptyline and nortriptyline.

The clinical effect of a sustained release preparation of amitriptyline has been compared with that of conventional amitriptyline tablets in a double-blind cross-over study with 24 patients suffering from endogenous depression. The sustained release preparation was given in a single evening dose (9 p.m.) of two thirds the total daily dose of conventional tablets, which was given in a three times-a-day regimen (8 a.m., 12 a.m. and 9 p.m.). Serum concentrations of amitriptyline and its active metabolite, nortriptyline, were determined. No difference was found between the two preparations as regards either clinical effect or side effects. No correlation could be shown between the clinical effects and the serum concentrations of amitriptyline and nortriptyline.

Adolescent↗

PubMed1990

Desipramine and nortriptyline antagonize apomorphine and reserpine hypothermia by a different mechanism.

The reversal of hypothermia, induced by reserpine or by a high (16 mg) dose of apomorphine, in male Swiss mice, does not seem to utilize a common mechanism. Desipramine (20 mg kg-1 i.p., 60 min) or nortriptyline (8 mg kg-1 i.p., 60 min) increased temperature in both reserpine (2.5 mg kg-1 s.c., 18-19 h) and apomorphine (16 mg kg-1 s.c., 30 min) treated mice. In apomorphine-treated animals the effect of both drugs was reversed by the mixed dopaminergic D1- D2-antagonist haloperidol (1 mg kg-1 i.p., 90 min), the D1-receptor blocking drug SCH 23390 (0.05 mg kg-1 s.c., 30 min), the alpha 1-adrenoceptor blocking drugs prazosin (3 mg kg-1 s.c., 90 min) and phenoxybenzamine (20 mg kg-1 i.p., 65 min), the beta-adrenoceptor blocking drug (+/-)-propranolol (10 mg kg-1 i.p., 120 min), and the opioid antagonist naloxone (2 mg kg-1 i.p., 15 min). In contrast the selective D2-antagonist (+/-)-sulpiride (100 mg kg-1 i.p., 90 min), and the alpha 2-antagonist yohimbine (2 mg kg-1 i.p., 75 min), failed to effect the reversal of apomorphine hypothermia brought about by desipramine or nortriptyline. Their temperature effects in reserpinized mice were not modified by any of the antagonists tested.

Animals↗

PubMed1980

Pharmacokinetic aspects on once-daily nortriptyline administration.

Steady state nortriptyline plasma levels have been studied in 21 endogenously depressed patients treated with a single 150-mg morning dose and compared to theoretical curves, calculated from previously known kinetic data. Fairly good agreement between predicted and experimentally found concentrations was observed. The fluctuation between maximal and minimal drug levels within the dosage interval was found to be more pronounced than with a t.i.d. dosage regimen, but still limited (mean ratio = 1.54; range = 1.0--2.16), and the minimum levels (mean = 102 ng/ml; range 46--250 ng/ml) were well compatible with published t.i.d. data. The biological half-life (mean = 39 h; range 24--86 h) agreed well with previously published data for volunteers. It is concluded that once-daily administration of nortriptyline results in relatively flat concentration curves as one would expect from the kinetic features of the drug. The clinical outcome is discussed in a separate paper.

Adult↗

PubMed1980

Therapeutic effect and side effects in patients with endogenous depression treated with oral nortriptyline once a day.

Out of 24 patients with endogenous depression, 21 completed the treatment with nortriptyline 150 mg as once-a-day dosage. The therapeutic effect was good and at any rate not inferior to that of dosages several times a day. Side effects were only little pronounced and at any rate not more marked than after dosages several times a day. Out of regard for the administrative and psychological advantages of the once-a-day dosage this form should be preferred, not least in the out-patient treatment with nortriptyline of endogenous depression.

Administration, Oral↗

PubMed1994

Effects of nortriptyline on heart rate variability in panic disorder patients: a preliminary study using power spectral analysis of heart rate.

Previous reports on heart rate variability suggest that, compared to controls, panic disorder patients have a higher relative mid-frequency (MF) (0.07-0.15 Hz) power in standing posture and that they also have a greater increase in standing MF power after the administration of yohimbine. We studied the effects of nortriptyline, a tricyclic antidepressant, on HR variability measures in 13 panic disorder patients before and after successful treatment. There was a highly significant increase in supine and standing HR (p = 0.00001) while there was a significant decrease of standing absolute and relative MF power (p = 0.009 and 0.0001 respectively). This uncontrolled preliminary study suggests a decrease in sympathetic activity related to nortriptyline treatment in addition to its anticholinergic effects.

Adult↗

PubMed1982

On the relationship between free plasma and saliva amitriptyline and nortriptyline.

Conflicting results on the correlation of tricyclic levels in plasma and saliva have raised doubts about the clinical usefulness of monitoring these drugs in the latter body fluid. However, saliva drug levels may reflect the free plasma concentration, which possibly determines its level in the brain. In two groups of depressive patients, the evolution was studied of the levels of amitriptyline and nortriptyline in plasma (as free and total) and in saliva, after the administration of amitriptyline. The results show a poor correlation between total plasma and saliva concentration of amitriptyline and nortriptyline, respectively. Levels of both tricyclics in saliva exceed by far those measured in plasma dialysate. However, the relationship is such that free plasma concentrations may be predicted from those measured in saliva, if one takes into account saliva pH at the moment of collecting the sample.

Amitriptyline↗