U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C17H14Cl2F2N2O3
Molecular Weight 403.208
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ROFLUMILAST

SMILES

C1CC1COc2cc(ccc2OC(F)F)C(=O)N=c3c(c[nH]cc3Cl)Cl

InChI

InChIKey=MNDBXUUTURYVHR-UHFFFAOYSA-N
InChI=1S/C17H14Cl2F2N2O3/c18-11-6-22-7-12(19)15(11)23-16(24)10-3-4-13(26-17(20)21)14(5-10)25-8-9-1-2-9/h3-7,9,17H,1-2,8H2,(H,22,23,24)

HIDE SMILES / InChI
Molecular Formula C17H14Cl2F2N2O3
Molecular Weight 403.208
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: description was created based on several sources, including http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002398/WC500103075.pdf

Roflumilast is a specific phosphodiesterase type (4PDE4) inhibitor indicated for use as a treatment to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations.

CNS Activity

CNS Penetrant
2344
Curator's Comment:: Studies in rats with radiolabeled roflumilast indicate low penetration across the blood-brain barrier.

Originator

Approval Year

2011
553
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
7728
 0.8 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Secondary
Approved
8043
DALIRESP

Approved Use

Indicated as a treatment to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. Limitations of Use: DALIRESP is not a bronchodilator and is not indicated for the relief of acute bronchospasm.

Launch Date

1.29885117E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
12.5 ng/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/30538429
0.5 mg single, oral
dose: 0.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ROFLUMILAST plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
65.1 ng × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/30538429
0.5 mg single, oral
dose: 0.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ROFLUMILAST plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
19.9 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/30538429
0.5 mg single, oral
dose: 0.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ROFLUMILAST plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
17 h
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022522s003lbl.pdf
ROFLUMILAST plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022522s003lbl.pdf
ROFLUMILAST plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
450 ug 1 times / day steady, oral
Recommended
Dose: 450 ug, 1 times / day
Route: oral
Route: steady
Dose: 450 ug, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022522s000lbl.pdf
unhealthy, 64 years (range: 40-91 years)
n = 4438
Health Status: unhealthy
Condition: COPD
Age Group: 64 years (range: 40-91 years)
Sex: M+F
Population Size: 4438
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022522s000lbl.pdf
Disc. AE: Diarrhea, Nausea...
AEs leading to
discontinuation/dose reduction:
Diarrhea (2.4%)
Nausea (1.6%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022522s000lbl.pdf
5000 ug single, oral
Highest studied dose
Dose: 5000 ug
Route: oral
Route: single
Dose: 5000 ug
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022522s000lbl.pdf
healthy, adult
n = 1
Health Status: healthy
Age Group: adult
Population Size: 1
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022522s000lbl.pdf
Other AEs: Headache, Gastrointestinal disorders...
Other AEs:
Headache (1 patient)
Gastrointestinal disorders (1 patient)
Dizziness (1 patient)
Palpitations (1 patient)
Lightheadedness (1 patient)
Clamminess (1 patient)
Arterial hypotension (1 patient)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022522s000lbl.pdf
AEs

AEs

AESignificanceDosePopulation
Nausea 1.6%
Disc. AE
450 ug 1 times / day steady, oral
Recommended
Dose: 450 ug, 1 times / day
Route: oral
Route: steady
Dose: 450 ug, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022522s000lbl.pdf
unhealthy, 64 years (range: 40-91 years)
n = 4438
Health Status: unhealthy
Condition: COPD
Age Group: 64 years (range: 40-91 years)
Sex: M+F
Population Size: 4438
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022522s000lbl.pdf
Diarrhea 2.4%
Disc. AE
450 ug 1 times / day steady, oral
Recommended
Dose: 450 ug, 1 times / day
Route: oral
Route: steady
Dose: 450 ug, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022522s000lbl.pdf
unhealthy, 64 years (range: 40-91 years)
n = 4438
Health Status: unhealthy
Condition: COPD
Age Group: 64 years (range: 40-91 years)
Sex: M+F
Population Size: 4438
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022522s000lbl.pdf
Arterial hypotension 1 patient
5000 ug single, oral
Highest studied dose
Dose: 5000 ug
Route: oral
Route: single
Dose: 5000 ug
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022522s000lbl.pdf
healthy, adult
n = 1
Health Status: healthy
Age Group: adult
Population Size: 1
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022522s000lbl.pdf
Clamminess 1 patient
5000 ug single, oral
Highest studied dose
Dose: 5000 ug
Route: oral
Route: single
Dose: 5000 ug
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022522s000lbl.pdf
healthy, adult
n = 1
Health Status: healthy
Age Group: adult
Population Size: 1
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022522s000lbl.pdf
Dizziness 1 patient
5000 ug single, oral
Highest studied dose
Dose: 5000 ug
Route: oral
Route: single
Dose: 5000 ug
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022522s000lbl.pdf
healthy, adult
n = 1
Health Status: healthy
Age Group: adult
Population Size: 1
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022522s000lbl.pdf
Gastrointestinal disorders 1 patient
5000 ug single, oral
Highest studied dose
Dose: 5000 ug
Route: oral
Route: single
Dose: 5000 ug
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022522s000lbl.pdf
healthy, adult
n = 1
Health Status: healthy
Age Group: adult
Population Size: 1
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022522s000lbl.pdf
Headache 1 patient
5000 ug single, oral
Highest studied dose
Dose: 5000 ug
Route: oral
Route: single
Dose: 5000 ug
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022522s000lbl.pdf
healthy, adult
n = 1
Health Status: healthy
Age Group: adult
Population Size: 1
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022522s000lbl.pdf
Lightheadedness 1 patient
5000 ug single, oral
Highest studied dose
Dose: 5000 ug
Route: oral
Route: single
Dose: 5000 ug
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022522s000lbl.pdf
healthy, adult
n = 1
Health Status: healthy
Age Group: adult
Population Size: 1
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022522s000lbl.pdf
Palpitations 1 patient
5000 ug single, oral
Highest studied dose
Dose: 5000 ug
Route: oral
Route: single
Dose: 5000 ug
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022522s000lbl.pdf
healthy, adult
n = 1
Health Status: healthy
Age Group: adult
Population Size: 1
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022522s000lbl.pdf
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1601
inhibitor
1604

inducer
355

substrate
936
inhibitor
1702

substrate
1118
inhibitor
1475

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A2
1383

CYP2A6
627

CYP2B6
717

CYP2C8
818

CYP2C19
1325

CYP2E1
790

CYP3A4/5
241

CYP4A9/11
30

P-gp
1330
CYP1A2
972

P-gp
1400

CYP1A1
325

CYP2A6
485

CYP2B6
616

CYP2C8
634

CYP2C19
910

CYP2E1
606

CYP3A5
367
CYP1A2
637

CYP2A6
77

CYP2C19
269

CYP3A4/5
108

CYP2B6
501

CYP2B1/2
1

CYP3A1/2
3

CYP4A1
17

CYP4A3
5
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP1A2
1532
 no
CYP1A2
1532
 no
CYP2A6
659
 no
CYP2A6
659
 no
CYP2B1/2
4
 no
CYP2B6
884
 no
CYP2C19
1392
 no
CYP2C19
1392
 no
CYP2C8
865
 no
CYP2C9
1648
 no
CYP2C9
1648
 no
CYP2D6
1738
 no
CYP2E1
871
 no
CYP3A1/2
4
 no
CYP3A4/5
293
 no
CYP3A4/5
293
 no
CYP4A1
24
 no
CYP4A3
5
 no
CYP4A9/11
30
 no
P-gp
1514
 no
CYP2B6
884
 weak
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP1A2
972
 major
yes (co-administration study)
Comment: fluvoxamine increased roflumilast cmax 12%, auc 156%; enoxacin increased roflumilast cmax 20%, auc 56%; cimetadine increased roflumilast cmax 46%, auc 85%
Page: 3.0
CYP3A4
1601
 major
yes (co-administration study)
Comment: erythromycin increased roflumilast cmax 40% and auc 70%; ketoconazole increased roflumilast cmax 23%, auc 99%; rifampicin decreased roflumilast cmax 68%, auc 80%
Page: 3.0
CYP1A1
325
 no
CYP2A6
485
 no
CYP2B6
616
 no
CYP2C19
910
 no
CYP2C8
634
 no
CYP2C9
936
 no
CYP2D6
1118
 no
CYP2E1
606
 no
CYP3A5
367
 no
P-gp
1400
 no
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1507
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:47657
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:47657
ChemicalBook
CB7412688
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7412688
MolPort
MolPort-006-069-128
https://www.molport.com/shop/molecule-link/MolPort-006-069-128
Selleck Chemicals
Roflumilast(Daxas)
http://www.selleckchem.com/products/Roflumilast(Daxas).html
ZINC
ZINC000000592419
http://zinc15.docking.org/substances/ZINC000000592419
eMolecules
6760347
https://www.emolecules.com/cgi-bin/more?vid=6760347
PubMed

PubMed

TitleDatePubMed
Roflumilast for asthma and chronic obstructive pulmonary disease.
2005 Oct
Phosphodiesterase 4 inhibitors for the treatment of asthma and COPD.
2006
Phosphodiesterase type 4 inhibitors cause proinflammatory effects in vivo.
2006 Oct
Treating COPD with PDE 4 inhibitors.
2007
Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD.
2007 Dec
Effects of roflumilast, a phosphodiesterase-4 inhibitor, on hypoxia- and monocrotaline-induced pulmonary hypertension in rats.
2009 Jul
Quinolines as a novel structural class of potent and selective PDE4 inhibitors: optimisation for oral administration.
2009 Mar 1
[Pharmacological profile of roflumilast].
2010 Dec
Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease.
2011 May 11
Simultaneous quantitation of IC87114, roflumilast and its active metabolite roflumilast N-oxide in plasma by LC-MS/MS: application for a pharmacokinetic study.
2012 Dec
Roflumilast inhibits the release of chemokines and TNF-α from human lung macrophages stimulated with lipopolysaccharide.
2012 Mar
The molecular basis for the inhibition of phosphodiesterase-4D by three natural resveratrol analogs. Isolation, molecular docking, molecular dynamics simulations, binding free energy, and bioassay.
2013 Oct
Patents

Patents

07470791
1
07678363
5
08536206
1
08604064
1
08618142
1
08741319
1
JP2002538207A
2
JP2002543133A
1
JP2006508994A
3
JP2006528229A
10
JP2007016024A
1
JP2007500148A
7
JP2007512223A
2
JP2007520507A
9
JP2007520538A
2
JP2008508360A
1
JP2010513276A
4
JP2012500252A
4
JP2012500794A
9
JP2013237683A
1
JP4532115B2
9
JP4700014B2
1
JP4742026B2
1
JP5349302B2
1

Sample Use Guides

In Vivo Use Guide
The recommended dosage for patients with COPD is one 500 ug tablet per day, with or without food.
Route of Administration: Oral
In Vitro Use Guide
To study the potency of roflumilast to inhibit adhesion of PMNL (polymorphonuclear leukocytes isolated from human peripheral venous blood) to TNFa-prestimulated HUVEC (human umbilical vein endothelial cells isolated from human umbilical cords) endothelial cell monolayers were stimulated with 0.3 ng/ml1 TNFa for 3 h. Medium was removed and roflumilast (10 pM–1 mM) was added followed by PMNL (50 000 cells per well) addition for 30 min. Roflumilast reduced adherence of PMNL to HUVEC with IC50 of 3.2 nM.
Substance Class Chemical
Created
by admin
on Sat Jun 26 08:02:59 UTC 2021
Edited
by admin
on Sat Jun 26 08:02:59 UTC 2021
Record UNII
0P6C6ZOP5U
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ROFLUMILAST
DASH   EMA EPAR   INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
DAXAS
Brand Name English
3-CYCLOPROPYLMETHOXY-N-(3,5-DICHLOROPYRIDIN-4-YL)-4-(DIFLUOROMETHOXY)BENZAMIDE
Systematic Name English
ROFLUMILAST [MART.]
Common Name English
ROFLUMILAST [ORANGE BOOK]
Common Name English
ROFLUMILAST [JAN]
Common Name English
ROFLUMILAST [MI]
Common Name English
ROFLUMILAST [USAN]
Common Name English
B9302-107
Code English
DALIRESP
Brand Name English
ROFLUMILAST [VANDF]
Common Name English
BY-217
Code English
BYK20869
Code English
ROFLUMILAST [EMA EPAR]
Common Name English
ROFLUMILAST [INN]
Common Name English
B-9302-107
Code English
ROFLUMILAST [WHO-DD]
Common Name English
BY217
Code English
BYK-20869
Code English
BENZAMIDE, 3-(CYCLOPROPYLMETHOXY)-N-(3,5-DICHLORO-4-PYRIDINYL)-4-(DIFLUOROMETHOXY)-
Systematic Name English
Classification Tree Code System Code
WHO-ATC R03DX07
Created by admin on Sat Jun 26 08:02:59 UTC 2021 , Edited by admin on Sat Jun 26 08:02:59 UTC 2021
LIVERTOX 859
Created by admin on Sat Jun 26 08:02:59 UTC 2021 , Edited by admin on Sat Jun 26 08:02:59 UTC 2021
EMA ASSESSMENT REPORTS DAXAS (AUTHORIZED: PULMONARY DISEASE, CHRONIC OBSTRUCTIVE )
Created by admin on Sat Jun 26 08:02:59 UTC 2021 , Edited by admin on Sat Jun 26 08:02:59 UTC 2021
WHO-VATC QR03DX07
Created by admin on Sat Jun 26 08:02:59 UTC 2021 , Edited by admin on Sat Jun 26 08:02:59 UTC 2021
NDF-RT N0000182961
Created by admin on Sat Jun 26 08:02:59 UTC 2021 , Edited by admin on Sat Jun 26 08:02:59 UTC 2021
NCI_THESAURUS C744
Created by admin on Sat Jun 26 08:02:59 UTC 2021 , Edited by admin on Sat Jun 26 08:02:59 UTC 2021
EMA ASSESSMENT REPORTS DALIRESP (AUTHORIZED: PULMONARY DISEASE, CHRONIC OBSTRUCTIVE )
Created by admin on Sat Jun 26 08:02:59 UTC 2021 , Edited by admin on Sat Jun 26 08:02:59 UTC 2021
EMA ASSESSMENT REPORTS LIBERTEK (AUTHORIZED: PULMONARY DISEASE, CHRONIC OBSTRUCTIVE)
Created by admin on Sat Jun 26 08:02:59 UTC 2021 , Edited by admin on Sat Jun 26 08:02:59 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C76890
Created by admin on Sat Jun 26 08:02:59 UTC 2021 , Edited by admin on Sat Jun 26 08:02:59 UTC 2021
PRIMARY
INN
7598
Created by admin on Sat Jun 26 08:02:59 UTC 2021 , Edited by admin on Sat Jun 26 08:02:59 UTC 2021
PRIMARY
IUPHAR
6962
Created by admin on Sat Jun 26 08:02:59 UTC 2021 , Edited by admin on Sat Jun 26 08:02:59 UTC 2021
PRIMARY
CAS
162401-32-3
Created by admin on Sat Jun 26 08:02:59 UTC 2021 , Edited by admin on Sat Jun 26 08:02:59 UTC 2021
PRIMARY
FDA UNII
0P6C6ZOP5U
Created by admin on Sat Jun 26 08:02:59 UTC 2021 , Edited by admin on Sat Jun 26 08:02:59 UTC 2021
PRIMARY
EPA CompTox
162401-32-3
Created by admin on Sat Jun 26 08:02:59 UTC 2021 , Edited by admin on Sat Jun 26 08:02:59 UTC 2021
PRIMARY
MESH
C424423
Created by admin on Sat Jun 26 08:02:59 UTC 2021 , Edited by admin on Sat Jun 26 08:02:59 UTC 2021
PRIMARY
WIKIPEDIA
ROFLUMILAST
Created by admin on Sat Jun 26 08:02:59 UTC 2021 , Edited by admin on Sat Jun 26 08:02:59 UTC 2021
PRIMARY
MERCK INDEX
M9648
Created by admin on Sat Jun 26 08:02:59 UTC 2021 , Edited by admin on Sat Jun 26 08:02:59 UTC 2021
PRIMARY Merck Index
NDF-RT
N0000182960
Created by admin on Sat Jun 26 08:02:59 UTC 2021 , Edited by admin on Sat Jun 26 08:02:59 UTC 2021
PRIMARY Phosphodiesterase 4 Inhibitors [MoA]
DRUG CENTRAL
3531
Created by admin on Sat Jun 26 08:02:59 UTC 2021 , Edited by admin on Sat Jun 26 08:02:59 UTC 2021
PRIMARY
DRUG BANK
DB01656
Created by admin on Sat Jun 26 08:02:59 UTC 2021 , Edited by admin on Sat Jun 26 08:02:59 UTC 2021
PRIMARY
RXCUI
1091836
Created by admin on Sat Jun 26 08:02:59 UTC 2021 , Edited by admin on Sat Jun 26 08:02:59 UTC 2021
PRIMARY RxNorm
ChEMBL
CHEMBL193240
Created by admin on Sat Jun 26 08:02:59 UTC 2021 , Edited by admin on Sat Jun 26 08:02:59 UTC 2021
PRIMARY
LACTMED
Roflumilast
Created by admin on Sat Jun 26 08:02:59 UTC 2021 , Edited by admin on Sat Jun 26 08:02:59 UTC 2021
PRIMARY
EVMPD
SUB10358MIG
Created by admin on Sat Jun 26 08:02:59 UTC 2021 , Edited by admin on Sat Jun 26 08:02:59 UTC 2021
PRIMARY
PUBCHEM
449193
Created by admin on Sat Jun 26 08:02:59 UTC 2021 , Edited by admin on Sat Jun 26 08:02:59 UTC 2021
PRIMARY
Related Record Type Details
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
Structure of ROFLUMILAST
EXCRETED UNCHANGED
The major route of elimination for roflumilast is through hepatic metabolism. Roflumilast was not detectable in urine. Roflumilast N-oxide was only a trace metabolite in urine (less than 1%).
URINE
CYTOCHROME P450 2C19
METABOLIC ENZYME -> SUBSTRATE
CYTOCHROME P450 1A2
METABOLIC ENZYME -> SUBSTRATE
CAMP-SPECIFIC 3',5'-CYCLIC PHOSPHODIESTERASE 4A
TARGET -> INHIBITOR
Related Record Type Details
Structure of N-(3,5-DICHLORO-4-PYRIDINYL)-4-(DIFLUOROMETHOXY)-3-HYDROXYBENZAMIDE
METABOLITE -> PARENT
Structure of ROFLUMILAST N-OXIDE
METABOLITE ACTIVE -> PARENT
MAJOR
Structure of 4-AMINO-3,5-DICHLOROPYRIDINE N-OXIDE
METABOLITE INACTIVE -> PARENT
conjugated metabolite
Related Record Type Details
Structure of ROFLUMILAST
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
NIH
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