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

Details

Stereochemistry ABSOLUTE
Molecular Formula C19H25NOS
Molecular Weight 315.473
Optical Activity ( - )
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ROTIGOTINE

SMILES

CCCN(CCC1=CC=CS1)[C@H]2CCC3=C(C2)C=CC=C3O

InChI

InChIKey=KFQYTPMOWPVWEJ-INIZCTEOSA-N
InChI=1S/C19H25NOS/c1-2-11-20(12-10-17-6-4-13-22-17)16-8-9-18-15(14-16)5-3-7-19(18)21/h3-7,13,16,21H,2,8-12,14H2,1H3/t16-/m0/s1

HIDE SMILES / InChI

Molecular Formula C19H25NOS
Molecular Weight 315.473
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including: https://www.drugs.com/mtm/rotigotine-transdermal.html http://www.rxlist.com/neupro-drug.htm http://www.wikidoc.org/index.php/Rotigotine

Rotigotine is an agonist at all 5 dopamine receptor subtypes (D1-D5) but binds to the D3 receptor with the highest affinity. It is also an antagonist at α-2-adrenergic receptors and an agonist at the 5HT1A receptors. Rotigotine also inhibits dopamine uptake and prolactin secretion. It is FDA approved for the treatment of Parkinson's disease, restless legs syndrome. Dopamine antagonists, such as antipsychotics or metoclopramide, may diminish the effectiveness of Rotigotine. Common adverse reactions include nausea, vomiting, somnolence, application site reactions, dizziness, anorexia, hyperhidrosis, insomnia and dyskinesia.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
NEUPRO

Approved Use

NEUPRO is a dopamine agonist indicated for the treatment of: Parkinson's disease (1.1) Moderate-to-severe primary Restless Legs Syndrome (1.2) 1.1 Parkinson's Disease (PD) NEUPRO is indicated for the treatment of Parkinson's disease. 1.2 Restless Legs Syndrome (RLS) NEUPRO is indicated for the treatment of moderate-to-severe primary Restless Legs Syndrome.

Launch Date

2007
Primary
NEUPRO

Approved Use

NEUPRO is a dopamine agonist indicated for the treatment of: Parkinson's disease (1.1) Moderate-to-severe primary Restless Legs Syndrome (1.2) 1.1 Parkinson's Disease (PD) NEUPRO is indicated for the treatment of Parkinson's disease. 1.2 Restless Legs Syndrome (RLS) NEUPRO is indicated for the treatment of moderate-to-severe primary Restless Legs Syndrome.

Launch Date

2007
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0.34 ng/mL
3 mg 2 times / day steady-state, transdermal
dose: 3 mg
route of administration: Transdermal
experiment type: STEADY-STATE
co-administered:
ROTIGOTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
4.63 ng × h/mL
3 mg 2 times / day steady-state, transdermal
dose: 3 mg
route of administration: Transdermal
experiment type: STEADY-STATE
co-administered:
ROTIGOTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
6.5 h
3 mg 2 times / day steady-state, transdermal
dose: 3 mg
route of administration: Transdermal
experiment type: STEADY-STATE
co-administered:
ROTIGOTINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
10%
unknown
ROTIGOTINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
54 mg 1 times / day multiple, topical
Highest studied dose
unhealthy, 29 - 88
n = 130
Health Status: unhealthy
Condition: Advanced-stage Parkinson’s disease
Age Group: 29 - 88
Sex: M+F
Population Size: 130
Sources: Page: p.10
24 mg 1 times / day multiple, topical
Studied dose
Dose: 24 mg, 1 times / day
Route: topical
Route: multiple
Dose: 24 mg, 1 times / day
Sources: Page: p.196
unhealthy, 68.8
n = 26
Health Status: unhealthy
Condition: Advanced-stage Parkinson’s disease
Age Group: 68.8
Sex: M+F
Population Size: 26
Sources: Page: p.196
Disc. AE: Abnormal ECG, Hypertension...
AEs leading to
discontinuation/dose reduction:
Abnormal ECG (mild, 3.85%)
Hypertension (mild, 3.85%)
Sensory hallucinations (moderate, 3.85%)
Application site reaction (moderate, 7.7%)
Sources: Page: p.196
8 mg 1 times / day multiple, topical
Recommended
Dose: 8 mg, 1 times / day
Route: topical
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Advanced-stage Parkinson’s disease
Sources: Page: p.1
Disc. AE: Allergic reaction, Somnolence...
AEs leading to
discontinuation/dose reduction:
Allergic reaction
Somnolence
Hallucinations
Psychotic behavior
Dyskinesia
Hypotension symptomatic
Syncope
Blood pressure increased
Tachycardia
Impulse-control disorder
Compulsive personality disorder
Daytime sleepiness
Sources: Page: p.1
8 mg 1 times / day multiple, topical
Recommended
Dose: 8 mg, 1 times / day
Route: topical
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1, p.5
unhealthy
Health Status: unhealthy
Condition: Advanced-stage Parkinson’s disease
Sources: Page: p.1, p.5
Disc. AE: Application site reaction...
AEs leading to
discontinuation/dose reduction:
Application site reaction (2%)
Sources: Page: p.1, p.5
AEs

AEs

AESignificanceDosePopulation
Abnormal ECG mild, 3.85%
Disc. AE
24 mg 1 times / day multiple, topical
Studied dose
Dose: 24 mg, 1 times / day
Route: topical
Route: multiple
Dose: 24 mg, 1 times / day
Sources: Page: p.196
unhealthy, 68.8
n = 26
Health Status: unhealthy
Condition: Advanced-stage Parkinson’s disease
Age Group: 68.8
Sex: M+F
Population Size: 26
Sources: Page: p.196
Hypertension mild, 3.85%
Disc. AE
24 mg 1 times / day multiple, topical
Studied dose
Dose: 24 mg, 1 times / day
Route: topical
Route: multiple
Dose: 24 mg, 1 times / day
Sources: Page: p.196
unhealthy, 68.8
n = 26
Health Status: unhealthy
Condition: Advanced-stage Parkinson’s disease
Age Group: 68.8
Sex: M+F
Population Size: 26
Sources: Page: p.196
Sensory hallucinations moderate, 3.85%
Disc. AE
24 mg 1 times / day multiple, topical
Studied dose
Dose: 24 mg, 1 times / day
Route: topical
Route: multiple
Dose: 24 mg, 1 times / day
Sources: Page: p.196
unhealthy, 68.8
n = 26
Health Status: unhealthy
Condition: Advanced-stage Parkinson’s disease
Age Group: 68.8
Sex: M+F
Population Size: 26
Sources: Page: p.196
Application site reaction moderate, 7.7%
Disc. AE
24 mg 1 times / day multiple, topical
Studied dose
Dose: 24 mg, 1 times / day
Route: topical
Route: multiple
Dose: 24 mg, 1 times / day
Sources: Page: p.196
unhealthy, 68.8
n = 26
Health Status: unhealthy
Condition: Advanced-stage Parkinson’s disease
Age Group: 68.8
Sex: M+F
Population Size: 26
Sources: Page: p.196
Allergic reaction Disc. AE
8 mg 1 times / day multiple, topical
Recommended
Dose: 8 mg, 1 times / day
Route: topical
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Advanced-stage Parkinson’s disease
Sources: Page: p.1
Blood pressure increased Disc. AE
8 mg 1 times / day multiple, topical
Recommended
Dose: 8 mg, 1 times / day
Route: topical
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Advanced-stage Parkinson’s disease
Sources: Page: p.1
Compulsive personality disorder Disc. AE
8 mg 1 times / day multiple, topical
Recommended
Dose: 8 mg, 1 times / day
Route: topical
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Advanced-stage Parkinson’s disease
Sources: Page: p.1
Daytime sleepiness Disc. AE
8 mg 1 times / day multiple, topical
Recommended
Dose: 8 mg, 1 times / day
Route: topical
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Advanced-stage Parkinson’s disease
Sources: Page: p.1
Dyskinesia Disc. AE
8 mg 1 times / day multiple, topical
Recommended
Dose: 8 mg, 1 times / day
Route: topical
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Advanced-stage Parkinson’s disease
Sources: Page: p.1
Hallucinations Disc. AE
8 mg 1 times / day multiple, topical
Recommended
Dose: 8 mg, 1 times / day
Route: topical
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Advanced-stage Parkinson’s disease
Sources: Page: p.1
Hypotension symptomatic Disc. AE
8 mg 1 times / day multiple, topical
Recommended
Dose: 8 mg, 1 times / day
Route: topical
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Advanced-stage Parkinson’s disease
Sources: Page: p.1
Impulse-control disorder Disc. AE
8 mg 1 times / day multiple, topical
Recommended
Dose: 8 mg, 1 times / day
Route: topical
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Advanced-stage Parkinson’s disease
Sources: Page: p.1
Psychotic behavior Disc. AE
8 mg 1 times / day multiple, topical
Recommended
Dose: 8 mg, 1 times / day
Route: topical
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Advanced-stage Parkinson’s disease
Sources: Page: p.1
Somnolence Disc. AE
8 mg 1 times / day multiple, topical
Recommended
Dose: 8 mg, 1 times / day
Route: topical
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Advanced-stage Parkinson’s disease
Sources: Page: p.1
Syncope Disc. AE
8 mg 1 times / day multiple, topical
Recommended
Dose: 8 mg, 1 times / day
Route: topical
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Advanced-stage Parkinson’s disease
Sources: Page: p.1
Tachycardia Disc. AE
8 mg 1 times / day multiple, topical
Recommended
Dose: 8 mg, 1 times / day
Route: topical
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Advanced-stage Parkinson’s disease
Sources: Page: p.1
Application site reaction 2%
Disc. AE
8 mg 1 times / day multiple, topical
Recommended
Dose: 8 mg, 1 times / day
Route: topical
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1, p.5
unhealthy
Health Status: unhealthy
Condition: Advanced-stage Parkinson’s disease
Sources: Page: p.1, p.5
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no (co-administration study)
Comment: rotigone did not influence the transport of digoxin
Page: 50.0
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
minor [Km >1000 uM]
minor [Km >1000 uM]
no
no
no
no
no
no
no
no
yes
yes
yes
yes
yes
yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1.
1991 Apr 18
Affinity for dopamine D2, D3, and D4 receptors of 2-aminotetralins. Relevance of D2 agonist binding for determination of receptor subtype selectivity.
1996 Oct 11
Further characterization of structural requirements for ligands at the dopamine D(2) and D(3) receptor: exploring the thiophene moiety.
2002 Jul 4
Rotigotine transdermal patch in the treatment of Parkinson's disease and restless legs syndrome.
2007 Jun
[Restless-legs syndrome].
2008 Aug-Sep
Three-month subchronic intramuscular toxicity study of rotigotine-loaded microspheres in Cynomolgus monkeys.
2013 Feb
Patents

Sample Use Guides

Parkinson’s disease: Initially, 2 mg/24 hours for early-stage disease or 4 mg/24 hours for advanced-stage disease. The dose may be increased as needed by 2 mg/24 hours at weekly intervals, up to 6 mg/24 hours for earlystage disease and up to 8 mg/24 hours for advanced-stage disease. Restless Legs Syndrome: Initially, 1 mg/24 hours, increased as needed by 1 mg/24 hours at weekly intervals, up to 3 mg/24 hours.
Route of Administration: Transdermal
In Vitro Use Guide
The binding of [3H]N-0437 (specific activity 80.6 Ci/mmol) to calf caudate membranes is described. It was found that [3H]N-0437 binds with a high affinity (KD = 0.17 nM) and a low proportion of non-specific binding.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:43:47 GMT 2023
Edited
by admin
on Fri Dec 15 15:43:47 GMT 2023
Record UNII
87T4T8BO2E
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ROTIGOTINE
EMA EPAR   INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
ROTIGOTINE [USP MONOGRAPH]
Common Name English
ROTIGOTINE [EP MONOGRAPH]
Common Name English
NEUPRO
Brand Name English
ROTIGOTINE [MI]
Common Name English
rotigotine [INN]
Common Name English
ROTIGOTINE [VANDF]
Common Name English
ROTIGOTINE [EMA EPAR]
Common Name English
SPM 962
Code English
(6S)-6-(PROPYL(2-(2-THIENYL)ETHYL)AMINO)-5,6,7,8-TETRAHYDRO-1-NAPHTHALENOL
Systematic Name English
SPM-962
Code English
ROTIGOTINE [ORANGE BOOK]
Common Name English
(-)-(S)-5,6,7,8-TETRAHYDRO-6-(PROPYL(2-(2-THIENYL)ETHYL)AMINO)-1-NAPHTHOL
Systematic Name English
ROTIGOTINE [JAN]
Common Name English
ROTIGOTINE [USAN]
Common Name English
1-NAPHTHALENOL, 5,6,7,8-TETRAHYDRO-6-(PROPYL(2-(2-THIENYL)ETHYL)AMINO-(6S)-
Common Name English
ROTIGOTINE [MART.]
Common Name English
Rotigotine [WHO-DD]
Common Name English
LEGANTO
Brand Name English
ROTIGOTINE [USP-RS]
Common Name English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS NEUPRO (AUTHORIZED: PARKINSON DISEASE)
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
WHO-ATC N04BC09
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
EMA ASSESSMENT REPORTS NEUPRO (AUTHORIZED: RESTLESS LEGS SYNDROME)
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
EMA ASSESSMENT REPORTS LEGANTO (AUTHORIZED: RESTLESS LEGS SYNDROME)
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
WHO-VATC QN04BC09
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
NCI_THESAURUS C66884
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
EMA ASSESSMENT REPORTS LEGANTO (AUTHORIZED: PARKINSON DISEASE)
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
Code System Code Type Description
USAN
QQ-05
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
PRIMARY
IUPHAR
941
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
PRIMARY
SMS_ID
100000089581
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
PRIMARY
INN
7897
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
PRIMARY
PUBCHEM
59227
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
PRIMARY
DAILYMED
87T4T8BO2E
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
PRIMARY
DRUG BANK
DB05271
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
PRIMARY
FDA UNII
87T4T8BO2E
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
PRIMARY
RXCUI
616739
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
PRIMARY RxNorm
WIKIPEDIA
ROTIGOTINE
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
PRIMARY
EVMPD
SUB21254
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
PRIMARY
HSDB
8254
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
PRIMARY
LACTMED
Rotigotine
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
PRIMARY
RS_ITEM_NUM
1606060
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
PRIMARY
NCI_THESAURUS
C77566
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
PRIMARY
CAS
99755-59-6
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
PRIMARY
ChEMBL
CHEMBL1303
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
PRIMARY
MERCK INDEX
m9674
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
PRIMARY Merck Index
DRUG CENTRAL
2407
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
PRIMARY
EPA CompTox
DTXSID5046772
Created by admin on Fri Dec 15 15:43:47 GMT 2023 , Edited by admin on Fri Dec 15 15:43:47 GMT 2023
PRIMARY
Related Record Type Details
EXCRETED UNCHANGED
URINE
TARGET -> AGONIST
TARGET -> AGONIST
SHORT-ACTING
TARGET -> AGONIST
BINDER->LIGAND
BINDING
TARGET -> AGONIST
Related Record Type Details
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CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
METABOLITE -> PARENT
MINOR
URINE
METABOLITE -> PARENT
two UDP-glucuronosyltransferases catalyze the metabolism of rotigotine
METABOLITE -> PARENT
MAJOR
PLASMA; URINE
METABOLITE -> PARENT
MAJOR
PLASMA; URINE
METABOLITE -> PARENT
sulfotransferases
METABOLITE -> PARENT
MAJOR
PLASMA; URINE
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CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
below LOQ (300 dpm/ml)
MINOR
URINE
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
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IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Tmax PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC