Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C15H11I4NO4 |
Molecular Weight | 776.87 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
N[C@@H](CC1=CC(I)=C(OC2=CC(I)=C(O)C(I)=C2)C(I)=C1)C(O)=O
InChI
InChIKey=XUIIKFGFIJCVMT-LBPRGKRZSA-N
InChI=1S/C15H11I4NO4/c16-8-4-7(5-9(17)13(8)21)24-14-10(18)1-6(2-11(14)19)3-12(20)15(22)23/h1-2,4-5,12,21H,3,20H2,(H,22,23)/t12-/m0/s1
Molecular Formula | C15H11I4NO4 |
Molecular Weight | 776.87 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionSources: http://www.drugbank.ca/drugs/DB00451Curator's Comment: Description was created based on several sources, including
https://www.drugs.com/dosage/levothyroxine.html
Sources: http://www.drugbank.ca/drugs/DB00451
Curator's Comment: Description was created based on several sources, including
https://www.drugs.com/dosage/levothyroxine.html
Levothyroxine (T4) is a synthetically prepared levo isomer of thyroxine, the major hormone secreted from the thyroid gland. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form triiodothyronine (T3) which exerts a broad spectrum of stimulatory effects on cell metabolism. Thyroid hormone increases the metabolic rate of cells of all tissues in the body. In the fetus and newborn, thyroid hormone is important for the growth and development of all tissues including bones and the brain. In adults, thyroid hormone helps to maintain brain function, food metabolism, and body temperature, among other effects. The symptoms of thyroid deficiency relieved by levothyroxine include slow speech, lack of energy, weight gain, hair loss, dry thick skin and unusual sensitivity to cold. Levothyroxine acts like the endogenous thyroid hormone thyroxine (T4, a tetra-iodinated tyrosine derivative). In the liver and kidney, T4 is converted to T3, the active metabolite. In order to increase solubility, the thyroid hormones attach to thyroid hormone binding proteins, thyroxin-binding globulin, and thyroxin-binding prealbumin (transthyretin). Transport and binding to thyroid hormone receptors in the cytoplasm and nucleus then takes place. Thus by acting as a replacement for natural thyroxine, symptoms of thyroxine deficiency are relieved. Levothyroxine is used for use alone or in combination with antithyroid agents to treat hypothyroidism, goiter, chronic lymphocytic thyroiditis, myxedema coma, and stupor.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1860 Sources: http://www.drugbank.ca/drugs/DB00451 |
|||
Target ID: CHEMBL1947 Sources: http://www.drugbank.ca/drugs/DB00451 |
0.136 nM [EC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Synthroid Approved UseLevothyroxine tablets are used for the following indications:
Hypothyroidism
As replacement or supplemental therapy in congenital or acquired hypothyroidism of any etiology, except transient hypothyroidism during the recovery phase of subacute thyroiditis. Specific indications include: primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) hypothyroidism and subclinical hypothyroidism. Primary hypothyroidism may result from functional deficiency, primary atrophy, partial or total congenital absence of the thyroid gland, or from the effects of surgery, radiation, or drugs, with or without the presence of goiter.
Pituitary TSH Suppression
In the treatment or prevention of various types of euthyroid goiters, including thyroid nodules, subacute or chronic lymphocytic thyroiditis (Hashimoto’s thyroiditis), multinodular goiter and, as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well differentiated thyroid cancer. Launch Date2002 |
|||
Primary | Synthroid Approved UseLevothyroxine tablets are used for the following indications:
Hypothyroidism
As replacement or supplemental therapy in congenital or acquired hypothyroidism of any etiology, except transient hypothyroidism during the recovery phase of subacute thyroiditis. Specific indications include: primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) hypothyroidism and subclinical hypothyroidism. Primary hypothyroidism may result from functional deficiency, primary atrophy, partial or total congenital absence of the thyroid gland, or from the effects of surgery, radiation, or drugs, with or without the presence of goiter.
Pituitary TSH Suppression
In the treatment or prevention of various types of euthyroid goiters, including thyroid nodules, subacute or chronic lymphocytic thyroiditis (Hashimoto’s thyroiditis), multinodular goiter and, as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well differentiated thyroid cancer. Launch Date2002 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
76.64 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30153382 |
600 μg single, oral dose: 600 μg route of administration: Oral experiment type: SINGLE co-administered: |
LEVOTHYROXINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1764.14 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30153382 |
600 μg single, oral dose: 600 μg route of administration: Oral experiment type: SINGLE co-administered: |
LEVOTHYROXINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
6.2 day |
unknown, unknown |
LEVOTHYROXINE serum | Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
7.5 h |
unknown, unknown |
LEVOTHYROXINE serum | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
0.04% |
unknown, unknown |
LEVOTHYROXINE plasma | Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
5.7 mg 1 times / day single, oral Studied dose Dose: 5.7 mg, 1 times / day Route: oral Route: single Dose: 5.7 mg, 1 times / day Sources: |
healthy, 22 months n = 1 Health Status: healthy Age Group: 22 months Sex: M Population Size: 1 Sources: |
Other AEs: Hypertension, Tachycardia... Other AEs: Hypertension (grade 1) Sources: Tachycardia (grade 1) |
18 mg 1 times / day single, oral Studied dose Dose: 18 mg, 1 times / day Route: oral Route: single Dose: 18 mg, 1 times / day Sources: |
healthy, 30 months n = 1 Health Status: healthy Age Group: 30 months Sex: M Population Size: 1 Sources: |
Other AEs: Hyperthyroidism, Seizures... |
600 ug 1 times / day single, oral Studied dose Dose: 600 ug, 1 times / day Route: oral Route: single Dose: 600 ug, 1 times / day Sources: |
healthy, mean age 35 years n = 36 Health Status: healthy Age Group: mean age 35 years Sex: M+F Population Size: 36 Sources: |
Disc. AE: Alanine aminotransferase increased... AEs leading to discontinuation/dose reduction: Alanine aminotransferase increased (2.8%) Sources: |
50 ug steady, oral (total daily dose) Dose: 50 ug Route: oral Route: steady Dose: 50 ug Sources: |
unhealthy n = 30 Health Status: unhealthy Condition: Graves Disease Population Size: 30 Sources: |
Other AEs: Atrial fibrillation, Palpitations... Other AEs: Atrial fibrillation (serious, 1 patient) Sources: Palpitations (below serious, 3 patients) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Hypertension | grade 1 | 5.7 mg 1 times / day single, oral Studied dose Dose: 5.7 mg, 1 times / day Route: oral Route: single Dose: 5.7 mg, 1 times / day Sources: |
healthy, 22 months n = 1 Health Status: healthy Age Group: 22 months Sex: M Population Size: 1 Sources: |
Tachycardia | grade 1 | 5.7 mg 1 times / day single, oral Studied dose Dose: 5.7 mg, 1 times / day Route: oral Route: single Dose: 5.7 mg, 1 times / day Sources: |
healthy, 22 months n = 1 Health Status: healthy Age Group: 22 months Sex: M Population Size: 1 Sources: |
Hyperthyroidism | 18 mg 1 times / day single, oral Studied dose Dose: 18 mg, 1 times / day Route: oral Route: single Dose: 18 mg, 1 times / day Sources: |
healthy, 30 months n = 1 Health Status: healthy Age Group: 30 months Sex: M Population Size: 1 Sources: |
|
Seizures | 18 mg 1 times / day single, oral Studied dose Dose: 18 mg, 1 times / day Route: oral Route: single Dose: 18 mg, 1 times / day Sources: |
healthy, 30 months n = 1 Health Status: healthy Age Group: 30 months Sex: M Population Size: 1 Sources: |
|
Alanine aminotransferase increased | 2.8% Disc. AE |
600 ug 1 times / day single, oral Studied dose Dose: 600 ug, 1 times / day Route: oral Route: single Dose: 600 ug, 1 times / day Sources: |
healthy, mean age 35 years n = 36 Health Status: healthy Age Group: mean age 35 years Sex: M+F Population Size: 36 Sources: |
Palpitations | below serious, 3 patients | 50 ug steady, oral (total daily dose) Dose: 50 ug Route: oral Route: steady Dose: 50 ug Sources: |
unhealthy n = 30 Health Status: unhealthy Condition: Graves Disease Population Size: 30 Sources: |
Atrial fibrillation | serious, 1 patient | 50 ug steady, oral (total daily dose) Dose: 50 ug Route: oral Route: steady Dose: 50 ug Sources: |
unhealthy n = 30 Health Status: unhealthy Condition: Graves Disease Population Size: 30 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/15258100/ |
no | |||
no | ||||
weak | ||||
weak | ||||
yes [IC50 15.4 uM] | ||||
yes [IC50 3.3 uM] | ||||
yes [IC50 4.9 uM] | ||||
yes | ||||
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes | ||||
yes | ||||
Sources: https://go.drugbank.com/drugs/DB00451 |
yes |
PubMed
Title | Date | PubMed |
---|---|---|
Potent competitive interactions of some brominated flame retardants and related compounds with human transthyretin in vitro. | 2000 Jul |
|
Improved antibody coating protocol using a second antibody antiserum. Application to total thyroxin immunoassay. | 2001 |
|
Thyroid function of former opioid addicts on naltrexone treatment. | 2001 |
|
Short- and long-term results of total vs subtotal thyroidectomies in the surgical treatment of Graves' disease. | 2001 |
|
A case of pulmonary metastatic thyroid cancer complicated with Graves' disease. | 2001 Apr |
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Plasma concentrations of persistent organochlorines in relation to thyrotropin and thyroid hormone levels in women. | 2001 Apr |
|
Amyloid goiter as the initial manifestation of systemic amyloidosis due to familial mediterranean fever with homozygous MEFV mutation. | 2001 Apr |
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Alterations of cognitive functions induced by exogenous application of thyroid hormones in healthy men: a double-blind cross-over study using event-related brain potentials. | 2001 Apr |
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Short-term hyperthyroidism followed by transient pituitary hypothyroidism in a very low birth weight infant born to a mother with uncontrolled Graves' disease. | 2001 Apr |
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Evaluation of growth and hormonal status in patients referred to the International Fanconi Anemia Registry. | 2001 Apr |
|
[Prescription of thyroid function tests in adults as a function of clinical circumstances and of patient management]. | 2001 Apr 14 |
|
[Pregnancy (conception) in hyper- or hypothyroidism]. | 2001 Apr 14 |
|
[Hereditary thyroxin-binding globulin deficiency--changed thyroid function tests]. | 2001 Apr 30 |
|
Development of hypertensive status in NISAG rats reared by normotensive Wistar rats. | 2001 Aug |
|
Effect of treatment of hypothyroidism on the plasma concentrations of neuroactive steroids and homocysteine. | 2001 Aug |
|
Tall cell papillary thyroid carcinoma metastatic to femur: evidence for thyroid hormone synthesis within the femur. | 2001 Aug |
|
Confusion over levothyroxine settled. | 2001 Aug 15 |
|
Congenital hypothyroidism in a child with unsuspected familial dysalbuminemic hyperthyroxinemia caused by a mutation (R218H) in the human albumin gene. | 2001 Dec |
|
Characterization of human liver thermostable phenol sulfotransferase (SULT1A1) allozymes with 3,3',5-triiodothyronine as the substrate. | 2001 Dec |
|
The role of thyroid hormone administration in potential organ donors. | 2001 Dec |
|
Coronary bypass surgery in patients with Sheehan's syndrome. | 2001 Dec |
|
Bone mass after long-term euthyroidism in former hyperthyroid women treated with (131)I influence of menopausal status. | 2001 Fall |
|
Efficacy of high therapeutic doses of iodine-131 in patients with differentiated thyroid cancer and detectable serum thyroglobulin. | 2001 Feb |
|
Panhypopituitarism associated with severe retroperitoneal fibrosis. | 2001 Feb |
|
Generic substitution: issues for problematic drugs. | 2001 Jan |
|
[Thyroid carcinoma. Diagnosis--nonoperative therapy--after care]. | 2001 Jan 11 |
|
Amantadine-induced cortical myoclonus. | 2001 Jan 23 |
|
Thyroid hormone deficiency determines predisposition to catalepsy in rats. | 2001 Jul |
|
What is going on with levothyroxine. | 2001 Jul 9 |
|
[Treatment of euthyroid goiter in the elderly]. | 2001 Jul-Aug |
|
[Euthyroid Graves' disease (problems of diagnosis and treatment)]. | 2001 Jul-Aug |
|
Five-year mortality in men and women with atrial fibrillation. | 2001 Jun |
|
[Concentration of thyrotropic hormone and free thyroxin in children with Down's syndrome]. | 2001 Jun |
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Molecular cloning, expression, and characterization of a canine sulfotransferase that is a human ST1B2 ortholog. | 2001 Jun 1 |
|
Effect of levothyroxine on cardiac function and structure in subclinical hypothyroidism: a double blind, placebo-controlled study. | 2001 Mar |
|
[The changes of PCBs and PCDFs as well as symptoms in Yusho patients for 30 years]. | 2001 May |
|
Effect of levothyroxine administration time on serum TSH in elderly patients. | 2001 May |
|
Use of soy protein supplement and resultant need for increased dose of levothyroxine. | 2001 May-Jun |
|
Changes of plasma arginine-vasopressin level in patients with hyperthyroidism during treatment. | 2001 May-Jun |
|
Usefulness of recombinant human thyrotropin in the radiometabolic treatment of selected patients with thyroid cancer. | 2001 Nov |
|
Treatment of hypothyroidism. | 2001 Nov 15 |
|
Papillary carcinoma in thyroglossal duct cyst. | 2001 Nov-Dec |
|
Thyroid function test abnormalities in newly admitted psychiatric patients residing in an iodine-deficient area: patterns and clinical significance. | 2001 Oct |
|
The acute effect of calcium carbonate on the intestinal absorption of levothyroxine. | 2001 Oct |
|
Effect of 131 iodine therapy on the course of Graves' ophthalmopathy: a quantitative analysis of extraocular muscle volumes using orbital magnetic resonance imaging. | 2001 Oct |
|
Functional evidence for the presence of type II 5'-deiodinase in somatotropes and its adaptive role in hypothyroidism. | 2001 Oct |
|
Thyroid hormones modify susceptibility to lidocaine-kindling in rats. | 2001 Oct 19 |
|
[Screening for thyroid disease. Occurrence of hypothyroidism and hyperthyroidism in patients admitted to a geriatric department]. | 2001 Oct 8 |
|
Molecular cloning and sequence of Sparus aurata skeletal myosin light chains expressed in white muscle: developmental expression and thyroid regulation. | 2001 Sep |
|
Soluble Fas is increased in hyperthyroidism independent of the underlying thyroid disease. | 2001 Sep |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/dosage/levothyroxine.html
Usual Adult Dose for Hypothyroidism
Average full replacement dose: 1.7 mcg/kg/day (e.g., 100 to 125 mcg/day for a 70 kg adult) orally
Older patients may require less than 1 mcg/kg/day
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25447738
Addition of Levothyroxine at concentrations of 100-200 nM rescued rat cerebellar granule neurons (CGNs) from cell death in K5 in a dose-dependent manner. 200 nM T4 was also effective in maintaining the neurites of CGNs in K5.
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 15:16:27 GMT 2023
by
admin
on
Fri Dec 15 15:16:27 GMT 2023
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Record UNII |
Q51BO43MG4
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Record Status |
Validated (UNII)
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Record Version |
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14921-1
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73557-1
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21 CFR 520.1248
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21 CFR 862.1685
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WHO-ESSENTIAL MEDICINES LIST |
18.8
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83121-4
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53350-5
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21 CFR 862.1700
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83122-2
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3027-0
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21 CFR 862.1695
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Q51BO43MG4
Created by
admin on Fri Dec 15 15:16:27 GMT 2023 , Edited by admin on Fri Dec 15 15:16:27 GMT 2023
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m10840
Created by
admin on Fri Dec 15 15:16:27 GMT 2023 , Edited by admin on Fri Dec 15 15:16:27 GMT 2023
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PRIMARY | Merck Index | ||
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D013974
Created by
admin on Fri Dec 15 15:16:27 GMT 2023 , Edited by admin on Fri Dec 15 15:16:27 GMT 2023
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DTXSID8023214
Created by
admin on Fri Dec 15 15:16:27 GMT 2023 , Edited by admin on Fri Dec 15 15:16:27 GMT 2023
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SUB127246
Created by
admin on Fri Dec 15 15:16:27 GMT 2023 , Edited by admin on Fri Dec 15 15:16:27 GMT 2023
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5819
Created by
admin on Fri Dec 15 15:16:27 GMT 2023 , Edited by admin on Fri Dec 15 15:16:27 GMT 2023
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1365000
Created by
admin on Fri Dec 15 15:16:27 GMT 2023 , Edited by admin on Fri Dec 15 15:16:27 GMT 2023
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Related Record | Type | Details | ||
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TRANSPORTER -> SUBSTRATE | |||
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> SUBSTRATE |
Related Record | Type | Details | ||
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METABOLITE ACTIVE -> PARENT |
MAJOR
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PRODRUG -> METABOLITE ACTIVE |
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METABOLITE INACTIVE -> PARENT | |||
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METABOLITE ACTIVE -> PARENT |
Related Record | Type | Details | ||
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PARENT -> IMPURITY |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Volume of Distribution | PHARMACOKINETIC |
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ORAL BIOAVAILABILITY | PHARMACOKINETIC |
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ORAL SOLUTION PHARMACOKINETIC |
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Biological Half-life | PHARMACOKINETIC |
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T(3) PHARMACOKINETIC |
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