Nortriptylin

DEA NFLIS-Drug Category -> Antidepressants

Pharmaceuticals -> Tricyclic Antidepressants (TCAs)

Pharmaceuticals

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Metabolite of Amitryptiline

log Kow = 4.51

4.7

4.4

Antidepressants -> Tricyclic antidepressants (TCA)

Breast Feeding; Lactation; Milk, Human; Antidepressive Agents; Antidepressive Agents, Tricyclic

Pharmaceuticals

10.13

10.1

9.7

164.8 Ų [M+H]+ [CCS Type: DT; Buffer gas: N2; Ionization: ESI+; Dataset: Antidepressants]

165.77 Ų [M+H-H2O]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

164.5 Ų [M+H]+ [CCS Type: TW; Method: Major Mix IMS/Tof Calibration Kit (Waters)]

163.1 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

White to off-white powder; slight, characteristic odor /Nortriptyline hydrochloride/

Crystals from ether and ethanol, MP 213-215 °C. Soluble in ethanol, water, chlorofrom; sparingly soluble in methanol; practiacllyinsoluble in ether, acetone, benzne and in most other organic solvents. UV max (methanol): 240 nm (epsilon 13900) /Nortryiptyline hydrocloride/

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 38 reports by companies from 2 notifications to the ECHA C&L Inventory.

Warning

H302: Harmful if swallowed [Warning Acute toxicity, oral]

REACH registered substance: Nortriptyline (EC: 200-788-8)

Nortriptyline: Does not have an individual approval but may be used under an appropriate group standard

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including nortriptyline hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Nortriptyline hydrochloride/

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. /Nortriptyline hydrochloride/

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary. /Nortriptyline hydrochloride/

Store at 20 deg to 25 °C (68 deg to 77 °F)

Keep container tightly closed in a dry and well-ventilated place. Light sensitive. Keep in a dry place. /Nortriptyline hydrochloride/

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Avoid breathing dust; Environmental precautions: Do not let product enter drains; Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal. /Nortriptyline hydrochloride/

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber; Contaminated packaging: Dispose of as unused product. /Nortriptyline hydrochloride/

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection. /Nortriptyline hydrochloride/

Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday. /Nortriptyline hydrochloride/

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands. /Nortriptyline hydrochloride/

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

Eye/face protection: Safety glasses with side-shields conforming to EN166. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). /Nortriptyline hydrochloride/

Skin protection: Handle with gloves. /Nortriptyline hydrochloride/

Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace. /Nortriptyline hydrochloride/

Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator. For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). /Nortriptyline hydrochloride/

This case illustrates a pharmacokinetic interaction between the tricyclic antidepressant, nortriptyline, and the antituberculosis drug, rifampin. Higher than expected doses of nortriptyline were required to obtain a therapeutic drug level while the patient was receiving rifampin. Following the discontinuation of rifampin, the patient became drowsy and the serum nortriptyline levels rose precipitously into the toxic range.

A case of significant hypoglycemia has been reported in a type II diabetic patient maintained on chlorpropamide (250 mg/day), after the addition of nortriptyline (125 mg/day).

Using data from a therapeutic drug monitoring database, kinetic interactions between the neuroleptics zuclopenthixol and perphenazine and tricyclic antidepressives were studied. Out of 290 patients monitored for amitriptyline and 611 patients monitored for nortriptyline, 77 patients were comedicated with perphenazine and 50 patients with zuclopenthixol. Comedication with perphenazine incr the median steady-state serum concn to daily dose ratio (C/D) of nortriptyline by 30-45%, whereas the median C/D of amitriptyline was unaffected. On the contrary, median C/D values of nortriptyline and amitriptyline were not significantly influenced by comedication with zuclopenthixol.

Two cases are described in which a 33-yr-old woman and a 36-yr-old man developed adverse effects resulting from an interaction between valproic acid (valproate) and nortriptyline. The first patient was taking 25 mg/day nortriptyline and within 1 wk of the addition of valproic acid in doses up to 1000 mg/day, she developed marked tremulousness of her hands and fingers. The plasma level of nortriptyline was 393 ng/mL and that of valproic acid was 105 mg/L. Both drugs were stopped and tremulousness subsided over the next 2 days. The second patient was receiving 75 mg/day nortriptyline and up to 1250 mg/day valproic acid. A plasma level of nortriptyline was 345 ng/mL. The nortriptyline dosage was titrated down to 25 mg/day and a subsequent drug level was 82 ng/mL. Thioridazine and loxapine were given concomitantly.

For more Interactions (Complete) data for NORTRIPTYLINE (31 total), please visit the HSDB record page.

Liver test abnormalities have been reported to occur in up to 16% of patients being treated with tricyclic antidepressants, but elevations are uncommonly above 3 times the upper limit of normal. The aminotransferase abnormalities are usually mild, asymptomatic and transient, reversing even with continuation of medication. Rare instances of clinically apparent acute liver injury have been reported due to nortriptyline. The onset of jaundice is usually within 2 to 3 months of starting nortriptyline and the predominant enzyme pattern has been hepatocellular. Several acute instances of nortriptyline hepatotoxicity with marked elevations in serum aminotransferase levels and acute liver failure have been described. Signs and symptoms of hypersensitivity and autoimmunity are usually not present.

TERRESTRIAL FATE: Based on a classification scheme(1), a measured Koc value of 3236(2) indicates that nortriptyline is expected to have slight mobility in soil(SRC). The estimated pKa of nortriptyline is 10.47(3), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as a cation and cations do not volatilize. Nortriptyline is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.2X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(5). A half-life of 40.5 days using a loam soil incubated for 78 days(6) suggests that biodegradation may be an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), a measured Koc value of 3236(2) indicates that nortriptyline is expected to adsorb to suspended solids and sediment(SRC). An estimated pKa of 10.47(3) indicates nortriptyline will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water and moist soil surfaces are not expected to be an important fate processes(SRC). According to a classification scheme(4), an estimated BCF of 440(SRC), from its log Kow of 4.51(5) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is high(SRC). A half-life of 40.5 days using a loam soil incubated for 78 days(7) suggests that biodegradation may be an important environmental fate process in water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), nortriptyline, which has an estimated vapor pressure of 2.2X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase nortriptyline is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 0.74 hours(SRC), calculated from its rate constant of 1.7X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase nortriptyline may be removed from the air by wet and dry deposition(SRC). The hydrochloride salt of nortriptyline absorbs light at wavelengths 240 nm(4); therefore, nortriptyline is not expected to be susceptible to direct photolysis by sunlight since sunlight consists of wavelengths above 290 nm(SRC).

IDENTIFICATION AND USE: Nortriptyline is a tricyclic antidepressant. HUMAN EXPOSURE AND TOXICITY: Symptoms of overdose/poisoning include the following: arrhythmias, bundle branch block, cardiac arrest, hypotension, circulatory collapse, mydriasis, blurred vision, tachycardia, vasodilation, urinary retention, decreased gastrointestinal motility, decreased bronchial secretions, dry mucous membranes and skin, hypothermia, respiratory depression, seizures, abnormal tendon reflexes, disorientation, agitation, myoclonic jerks, coma and pyramidal signs. A woman with chronic obstructive pulmonary disease receiving nortriptyline experienced depression of CO2 sensitivity and ventilatory load compensation with a concomitant increase in exercise tolerance with decreased dyspnea. In other words, nortriptyline demonstrated a depressant effect on ventilatory control. Nortriptyline increases the risk for sudden cardiac arrest in the general population, particularly in the presence of genetic and/or non-genetic factors that decrease cardiac excitability by blocking the cardiac sodium channel. Antidepressant have been shown to increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. ANIMAL STUDIES: Dogs receiving nortriptyline hydrochloride orally for twelve months tolerated as much as 20 mg/kg/day. However, a large oral dose (40 mg per kg daily) caused signs of depression and ataxia and, with continued treatment, death at the end of the first month. In chronic toxicity studies, rats tolerated a concentration of nortriptyline hydrochloride in the diet equivalent to 150 mg/kg/day for one year. Rats showed some growth retardation but no visceral damage. Nortriptyline was tested for genotoxicity using the somatic mutation and recombination test (SMART) in wing cells of Drosophila melanogaster. The drug was not genotoxic at concentrations up to 100 mM.

Like many other TCAs, the toxicity of nortriptyline can be very harmful to the body. During an overdose, there is a blockade of the following receptors: sodium channels (fast) in the heart, muscarinic Ach receptors (central and peripheral), alpha-1 receptors in the periphery, and H1 and GABA-A in the central nervous system. Therefore, the most crucial initial step when assessing a patient with toxicity is ensuring the patient can adequately breathe. Intubation is usually mandatory for airway protection and proper ventilation. In addition, the clinician can administer IV fluids for hypotension.

It is believed that nortriptyline either inhibits the reuptake of the neurotransmitter serotonin at the neuronal membrane or acts at beta-adrenergic receptors. Tricyclic antidepressants do not inhibit monoamine oxidase nor do they affect dopamine reuptake.

Symptoms of overdose include cardiac dysrhythmias, severe hypotension, shock, congestive heart failure, pulmonary edema, convulsions, and CNS depression, including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity.

A log Koc of 3.51 (Kd = 117 L/kg), corresponding to a Koc of 3236, was measured using an agricultural soil (pH 6.3) from Corrstown, Co Dublin, Ireland(1). According to a classification scheme(2), this Koc value suggests that nortriptyline is expected to have slight mobility in soil. The estimated pKa of nortriptyline is 10.47(3), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). A Kd values of 600 L/kg hahes been reported using a digester sludge from wastewater treatment plant, Dublin Ireland (pH 6.3)(1).

/SIGNS AND SYMPTOMS/ Characteristics of acute tricyclic antidepressant poisoning: Cardiovascular effects: ventricular rate >120 beats/min, QRS duration >100 msec, arrhythmias, bundle branch block, cardiac arrest, hypotension, and circulatory collapse. /Tricyclic Antidepressants; From table/

/SIGNS AND SYMPTOMS/ Characteristics of acute tricyclic antidepressant poisoning: Anticholinergic effects: mydriasis, blurred vision, tachycardia, vasodilation, urinary retention, decreased gastrointestinal motility, decreased bronchial secretions, and dry mucous membranes and skin. /Tricyclic Antidepressants; From table/

/SIGNS AND SYMPTOMS/ ... In overdose, delayed conduction may lead to a complete heart block or ventricular reentry arrhythmias. Either of these complications, or a combo of both, may lead to death. ... /Tricyclic antidepressants/

/SIGNS AND SYMPTOMS/ The most crucial period for cardiac arrhythmias is the first 12 hr after ingestion. Even after the coma phase is terminated and neurologic signs appear normal, the chance for delayed life threatening cardiovascular toxicity, often unexpected, remains. Cardiovascular complications have been reported to onset as long as 6 days after ingestion, even after significant clinical improvement was noted. /Tricyclic Antidepressants/

For more Human Toxicity Excerpts (Complete) data for NORTRIPTYLINE (13 total), please visit the HSDB record page.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including nortriptyline hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Nortriptyline hydrochloride/

N - Nervous system

QN - Nervous system

Though prescribing information does not identify a specific mechanism of action for nortriptyline, is believed that nortriptyline either inhibits the reuptake of the neurotransmitter serotonin at the neuronal membrane or acts at the level of the beta-adrenergic receptors. It displays a more selective reuptake inhibition for noradrenaline, which may explain increased symptom improvement after nortriptyline therapy. Tricyclic antidepressants do not inhibit monoamine oxidase nor do they affect dopamine reuptake. As with other tricyclics, nortriptyline displays affinity for other receptors including mACh receptors, histamine receptors, 5-HT receptors, in addition to other receptors.

The mechanism of adverse imipramine-induced reactions ... was investigated by precipitating such reactions in rats with three injections (ip) of imipramine (5-40 mg/kg) at 24, 5, and 1 hr before testing, and comparing their occurrence with comparable treatments using specific noradrenergic and serotonergic reuptake inhibitors (nortriptyline (10 or 30 mg/kg, ip), citalopram (0.5-5.0 mg/kg, ip)). This initial study indicated that these reactions were mediated by imipramine's noradrenergic effects.

The effect of equal-dose regimens of amitriptyline and nortriptyline on the concn of serotonin, dopamine and major acidic metabolites was compared in 5 distinct brain regions as a function of inbred mouse strain. Amitriptyline incr to a greater extent the regional brain serotonin levels in the albino BALB/c mouse than did nortriptyline. Both drugs incr serotonin levels but decr cerebral 5-hydroxyindoleacetic acid levels in some distinct brain regions of the black C57BL/6 mouse strain. The results suggest a strain-dependent differential incr in brain serotonin turnover in specific mouse strain brain regions which may account for the greater incidence of amitriptyline-induced sedation and seizures. The BALB/c mouse was also found to be more sensitive than the C57BL/6 strain to the action of both drugs on dopamine and major acidic metabolites with amitriptyline showing more regional brain potency than nortriptyline. The data suggest an incr in dopamine turnover particularly in brain areas assoc with motor function and posture which may account for tricyclic antidepressant-induced extrapyramidal disorders. The results also indicate that the C57BL/6 mouse strain may be of experimental value for studying the mechanism underlying tricyclic-induced adverse reactions relevant to sedation and movement disorders as a function of genetic predisposition.

Neuropathic pain is pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. It is usually chronic and challenging to treat. Some antidepressants are first-line pharmacological treatments for neuropathic pain. The noradrenaline that is recruited by the action of the antidepressants on reuptake transporters has been proposed to act through beta2-adrenoceptors (beta2-ARs) to lead to the observed therapeutic effect. However, the complex downstream mechanism mediating this action remained to be identified. In this study, we demonstrate in a mouse model of neuropathic pain that an antidepressant's effect on neuropathic allodynia involves the peripheral nervous system and the inhibition of cytokine tumor necrosis factor a (TNFa) production. The antiallodynic action of nortriptyline is indeed lost after peripheral sympathectomy, but not after lesion of central descending noradrenergic pathways. More particularly, we report that antidepressant-recruited noradrenaline acts, within dorsal root ganglia, on beta2-ARs expressed by non-neuronal satellite cells. This stimulation of beta2-ARs decreases the neuropathy-induced production of membrane-bound TNFa, resulting in relief of neuropathic allodynia. This indirect anti-TNFa action was observed with the tricyclic antidepressant nortriptyline, the selective serotonin and noradrenaline reuptake inhibitor venlafaxine and the beta2-AR agonist terbutaline. Our data revealed an original therapeutic mechanism that may open novel research avenues for the management of painful peripheral neuropathies.

The average plasma half-life of nortriptyline in healthy volunteers is about 26 hours, but is said to range from 16 to 38 hours. One study mentions a mean half-life of about 39 hours.

The plasma half-life of nortriptyline ranges from 16 to more than 90 hours.

The clinical pharmacokinetics of amitriptyline were studied in four volunteers after the oral administration of 75 mg. ... The mean elimination half-life was 36.1 hours. ...

Nortriptyline is metabolized via demethylation and hydroxylation in the liver followed by glucuronic acid conjugation. CYP2D6 plays a large role in nortriptyline metabolism, with contributions from CYP1A2, CYP2C19 and CYP3A4. The main active metabolite is 10-hydroxynortriptyline exists in both cis and a trans form, with the trans form is higher in potency. 10-hydroxynortriptyline is the most frequently found in the plasma. Most of the other metabolites are conjugated, and are less potent.

Biotransformation of amitriptyline to its demethylated product nortriptyline was studied in vitro with human liver microsomes from four different donors, preselected to reflect a range of metabolic rates. Reaction velocity versus substrate concn was consistent with a sigmoid Vmax model. Vmax varied from 0.42 to 3.42 nmol/mg/min, Km from 33 to 89 uM amitriptyline. Ketoconazole was a highly potent inhibitor of N-demethylation, with a mean Ki value of 0.11 + or - 0.013 uM ... whereas quinidine (up to 50 uM), a CYP2D6 inhibitor, and alpha-naphthoflavone (up to 5 uM), a CYP1A2 inhibitor only at low concn, showed no effect. All selective serotonin reuptake inhibitors tested had an inhibitory effect on the formation of nortriptyline, with mean Ki values of 4.37 (+ or - 3.38) uM for sertraline, 5.46 (+ or - 1.95) uM for desmethylsertraline, 9.22 (+ or - 3.69) uM for fluvoxamine, 12.26 (+ or - 5.67) uM for norfluoxetine, 15.76 (+ or - 5.50) uM for paroxetine, and 43.55 (+ or - 18.28) uM for fluoxetine. A polyclonal rabbit antibody against rat liver CYP3A1, in antibody/microsomal protein ratios varying from 1:1 to 10:1, inhibited N-demethylation of amitriptyline to an asymptotic max of 60%.

The metabolic disposition of the antidepressants and antipsychotics has been reported to be significantly influenced by the cytochrome P450 (CYP) 2D6 isozyme. The two most studied antidepressants are amitriptyline and imipramine. Amitriptyline conversion to nortriptyline and nortriptyline metabolism to its 10-hydroxymetabolite were shown to be influenced by the 2D6 isozyme.

The stability of amitriptyline, nortriptyline, desipramine and imipramine in formalin-fixed human liver tissue and formalin soln was investigated. The levels of the tricyclic and its primary demethylated metabolite in the frozen liver were determined and compared with levels obtained in the formalin-fixed liver and formalin soln in which the liver was stored. It was obvious that some methylation of the secondary amine, nortriptyline, to the corresponding tertiary amine, amitriptyline, and of desipramine to imipramine took place in the formalin environment. Nortriptyline was not detected in most cases, suggesting that it may degrade more rapidly than desipramine. There was no consistent ratio between the concn of the drug in the frozen liver tissue versus formalin-preserved tissue or versus formalin soln. The methylation rates of the secondary amines could not be quantitated. Storage of the liver tissue in formalin at room temp resulted in leaching of the drugs into the formalin soln. The drugs tested may be detected for up to 22 mo in the formalin-fixed liver and in the formalin medium.

Nortriptyline has known human metabolites that include demethylnortriptyline and E-10-hydroxynortriptyline.

Undergoes hepatic metabolism via the same pathway as other TCAs. Route of Elimination: Approximately one-third of a single orally administered dose is excreted in urine within 24 hours. Small amounts are excreted in feces via biliary elimination. Half Life: 16 to 90+ hours

BL03SY4LXB

NORTRIPTYLINE

Established Pharmacologic Class [EPC] - Tricyclic Antidepressant

Nortriptyline is a Tricyclic Antidepressant.

Substances that contain a fused three-ring moiety and are used in the treatment of depression. These drugs block the uptake of norepinephrine and serotonin into axon terminals and may block some subtypes of serotonin, adrenergic, and histamine receptors. However, the mechanism of their antidepressant effects is not clear because the therapeutic effects usually take weeks to develop and may reflect compensatory changes in the central nervous system.

Drugs that block the transport of adrenergic transmitters into axon terminals or into storage vesicles within terminals. The tricyclic antidepressants (ANTIDEPRESSIVE AGENTS, TRICYCLIC) and amphetamines are among the therapeutically important drugs that may act via inhibition of adrenergic transport. Many of these drugs also block transport of serotonin.

Nortriptyline is readily absorbed in the gastrointestinal tract with extensive variation in plasma levels, depending on the patient. This drug undergoes first-pass metabolism and its plasma concentrations are attained within 7 to 8.5 hours after oral administration. The bioavailability of nortriptyline varies considerably and ranges from 45 to 85%.

Nortriptyline and its metabolites are mainly excreted in the urine, where only small amounts (2%) of the total drug is recovered as unchanged parent compound. Approximately one-third of a single orally administered dose is excreted in urine within 24 hours. Small amounts are excreted in feces via biliary elimination.

The apparent volume of distribution (Vd)β, estimated after intravenous administration is 1633 ± 268 L within the range of 1460 to 2030 (21 ± 4 L/kg). Nortriptyline crosses the placenta and is found in the breast milk. It distributes to the heart, lungs, brain, and the liver.

The average plasma clearance of nortriptyline in a study of healthy volunteers was 54 L/h. The average systemic clearance of nortriptyline is 30.6 ± 6.9 L / h, within the range of 18.6 to 39.6 L/hour.

/MILK/ Nortriptyline is distributed into milk. Nortriptyline concentrations in milk appear to be similar to or slightly greater than those present in maternal serum.

Peak plasma concentrations occur within 7-8.5 hours after oral administration. Optimal response to the drug appears to be associated with plasma concentrations of 50-150 ng/mL.

MEDICATION

Adrenergic Uptake Inhibitors; Antidepressive Agents, Tricyclic

Use (kg; approx.) in Germany (2009): >100

For the treatment of depression, chronic pain, irritable bowel syndrome, sleep disorders, diabetic neuropathy, agitation and insomnia, and migraine prophylaxis.

Table: Nortriptyline Hydrochloride Preparations [Table#4557]

Acetexa; Allegron; Aventyl; Noritren; Nortrilen; Pamelor; Sensaval; Vividyl. /Nortriptyline hydrochloride/

Pharmaceuticals -> Transformation products

Pharmaceuticals