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

Details

Stereochemistry ACHIRAL
Molecular Formula C24H29N7O2
Molecular Weight 447.5337
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PALBOCICLIB

SMILES

Cc1c2cnc(Nc3ccc(cn3)N4CCNCC4)nc2n(C5CCCC5)c(=O)c1C(=O)C

InChI

InChIKey=AHJRHEGDXFFMBM-UHFFFAOYSA-N
InChI=1S/C24H29N7O2/c1-15-19-14-27-24(28-20-8-7-18(13-26-20)30-11-9-25-10-12-30)29-22(19)31(17-5-3-4-6-17)23(33)21(15)16(2)32/h7-8,13-14,17,25H,3-6,9-12H2,1-2H3,(H,26,27,28,29)

HIDE SMILES / InChI

Molecular Formula C24H29N7O2
Molecular Weight 447.5337
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 https://www.drugbank.ca/drugs/DB09073

Palbociclib is an oral, reversible, selective, small-molecule inhibitor of CDK4 and CDK6 indicated in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. CDK4 and CDK6 along with their regulatory partner cyclin D1 play a key role in regulating the G1- to S-phase cell-cycle transition via regulation of phosphorylation of the retinoblastoma (Rb) protein. Inhibition of these proteins leads to reduced phosphorylation of Rb, inhibition of downstream signalling, and increased tumor growth arrest. Palbociclib received an accelerated approval from the Food and Drug Administration on February 3, 2015. Palbociclib is marketed under the trade name Ibrance. IBRANCE is a kinase inhibitor indicated in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease.

Originator

Curator's Comment:: # Onyx Pharmaceuticals; Pfizer

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
IBRANCE

Approved Use

IBRANCE is indicated in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. This indication is approved under accelerated approval based on progression-free survival (PFS)

Launch Date

1.42292156E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
104.1 ng/mL
125 mg single, oral
dose: 125 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PALBOCICLIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2483 ng × h/mL
125 mg single, oral
dose: 125 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PALBOCICLIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
23.9 h
125 mg single, oral
dose: 125 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PALBOCICLIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
150 mg 1 times / day multiple, oral
Highest studied dose
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 54 years (range: 22–77 years)
n = 3
Health Status: unhealthy
Age Group: 54 years (range: 22–77 years)
Sex: M+F
Population Size: 3
Sources:
125 mg 1 times / day steady, oral
MTD|RP2D
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy, 54 years (range: 22–77 years)
n = 22
Health Status: unhealthy
Age Group: 54 years (range: 22–77 years)
Sex: M+F
Population Size: 22
Sources:
DLT: Neutropenia...
Dose limiting toxicities:
Neutropenia (grade 3, 1 patient)
Sources:
150 mg 1 times / day steady, oral
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 54 years (range: 22–77 years)
n = 3
Health Status: unhealthy
Age Group: 54 years (range: 22–77 years)
Sex: M+F
Population Size: 3
Sources:
DLT: Neutropenia...
Dose limiting toxicities:
Neutropenia (grade 3-4, 2 patients)
Sources:
75 mg 1 times / day steady, oral
Dose: 75 mg, 1 times / day
Route: oral
Route: steady
Dose: 75 mg, 1 times / day
Sources:
unhealthy, 54 years (range: 22–77 years)
n = 7
Health Status: unhealthy
Age Group: 54 years (range: 22–77 years)
Sex: M+F
Population Size: 7
Sources:
DLT: Neutropenia...
Dose limiting toxicities:
Neutropenia (grade 3-4, 2 patients)
Sources:
125 mg 1 times / day steady, oral
Recommended
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Co-administed with::
letrozole(2.5 mg/day)
Sources:
unhealthy, 63 years (range: 38 - 89 years)
n = 83
Health Status: unhealthy
Age Group: 63 years (range: 38 - 89 years)
Sex: M+F
Population Size: 83
Sources:
Disc. AE: Neutropenia, Asthenia...
AEs leading to
discontinuation/dose reduction:
Neutropenia (6%)
Asthenia (1%)
Fatigue (1%)
Sources:
200 mg 1 times / day multiple, oral
Overdose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources: Page: p. 112
unhealthy, adult
n = 1
Health Status: unhealthy
Age Group: adult
Population Size: 1
Sources: Page: p. 112
Other AEs: Nausea, Vomiting...
Other AEs:
Nausea (1 patient)
Vomiting (1 patient)
Dizziness (1 patient)
Sources: Page: p. 112
250 mg 1 times / day multiple, oral
Overdose
Dose: 250 mg, 1 times / day
Route: oral
Route: multiple
Dose: 250 mg, 1 times / day
Sources: Page: p. 112
unhealthy, adult
n = 1
Health Status: unhealthy
Age Group: adult
Population Size: 1
Sources: Page: p. 112
Disc. AE: Neutropenia...
AEs leading to
discontinuation/dose reduction:
Neutropenia (grade 4, 1 patient)
Sources: Page: p. 112
AEs

AEs

AESignificanceDosePopulation
Neutropenia grade 3, 1 patient
DLT
125 mg 1 times / day steady, oral
MTD|RP2D
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Sources:
unhealthy, 54 years (range: 22–77 years)
n = 22
Health Status: unhealthy
Age Group: 54 years (range: 22–77 years)
Sex: M+F
Population Size: 22
Sources:
Neutropenia grade 3-4, 2 patients
DLT
150 mg 1 times / day steady, oral
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources:
unhealthy, 54 years (range: 22–77 years)
n = 3
Health Status: unhealthy
Age Group: 54 years (range: 22–77 years)
Sex: M+F
Population Size: 3
Sources:
Neutropenia grade 3-4, 2 patients
DLT
75 mg 1 times / day steady, oral
Dose: 75 mg, 1 times / day
Route: oral
Route: steady
Dose: 75 mg, 1 times / day
Sources:
unhealthy, 54 years (range: 22–77 years)
n = 7
Health Status: unhealthy
Age Group: 54 years (range: 22–77 years)
Sex: M+F
Population Size: 7
Sources:
Asthenia 1%
Disc. AE
125 mg 1 times / day steady, oral
Recommended
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Co-administed with::
letrozole(2.5 mg/day)
Sources:
unhealthy, 63 years (range: 38 - 89 years)
n = 83
Health Status: unhealthy
Age Group: 63 years (range: 38 - 89 years)
Sex: M+F
Population Size: 83
Sources:
Fatigue 1%
Disc. AE
125 mg 1 times / day steady, oral
Recommended
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Co-administed with::
letrozole(2.5 mg/day)
Sources:
unhealthy, 63 years (range: 38 - 89 years)
n = 83
Health Status: unhealthy
Age Group: 63 years (range: 38 - 89 years)
Sex: M+F
Population Size: 83
Sources:
Neutropenia 6%
Disc. AE
125 mg 1 times / day steady, oral
Recommended
Dose: 125 mg, 1 times / day
Route: oral
Route: steady
Dose: 125 mg, 1 times / day
Co-administed with::
letrozole(2.5 mg/day)
Sources:
unhealthy, 63 years (range: 38 - 89 years)
n = 83
Health Status: unhealthy
Age Group: 63 years (range: 38 - 89 years)
Sex: M+F
Population Size: 83
Sources:
Dizziness 1 patient
200 mg 1 times / day multiple, oral
Overdose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources: Page: p. 112
unhealthy, adult
n = 1
Health Status: unhealthy
Age Group: adult
Population Size: 1
Sources: Page: p. 112
Nausea 1 patient
200 mg 1 times / day multiple, oral
Overdose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources: Page: p. 112
unhealthy, adult
n = 1
Health Status: unhealthy
Age Group: adult
Population Size: 1
Sources: Page: p. 112
Vomiting 1 patient
200 mg 1 times / day multiple, oral
Overdose
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources: Page: p. 112
unhealthy, adult
n = 1
Health Status: unhealthy
Age Group: adult
Population Size: 1
Sources: Page: p. 112
Neutropenia grade 4, 1 patient
Disc. AE
250 mg 1 times / day multiple, oral
Overdose
Dose: 250 mg, 1 times / day
Route: oral
Route: multiple
Dose: 250 mg, 1 times / day
Sources: Page: p. 112
unhealthy, adult
n = 1
Health Status: unhealthy
Age Group: adult
Population Size: 1
Sources: Page: p. 112
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no [IC50 >30 uM]
no [IC50 >30 uM]
no [IC50 >30 uM]
no [IC50 >30 uM]
no [IC50 >30 uM]
no [IC50 >30 uM]
no [IC50 >30 uM]
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
weak
Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Primary care pediatrics vs. family practice: a nonissue.
1983 Aug
Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts.
2004 Nov
Pharmacologic inhibition of cyclin-dependent kinase 4/6 activity arrests proliferation in myoblasts and rhabdomyosarcoma-derived cells.
2006 May
Mantle cell lymphoma cells express predominantly cyclin D1a isoform and are highly sensitive to selective inhibition of CDK4 kinase activity.
2006 Sep 1
Stem cell factor and interleukin-2/15 combine to enhance MAPK-mediated proliferation of human natural killer cells.
2009 Mar 19
Epigenetic silencing of the tumor suppressor microRNA Hsa-miR-124a regulates CDK6 expression and confers a poor prognosis in acute lymphoblastic leukemia.
2009 May 15
A synthetic lethal interaction between K-Ras oncogenes and Cdk4 unveils a therapeutic strategy for non-small cell lung carcinoma.
2010 Jul 13
Proliferative suppression by CDK4/6 inhibition: complex function of the retinoblastoma pathway in liver tissue and hepatoma cells.
2010 May
Quantitative analysis of PD 0332991 in xenograft mouse tumor tissue by a 96-well supported liquid extraction format and liquid chromatography/mass spectrometry.
2010 Nov 2
RB-pathway disruption in breast cancer: differential association with disease subtypes, disease-specific prognosis and therapeutic response.
2010 Oct 15
A bioinformatical and functional approach to identify novel strategies for chemoprevention of colorectal cancer.
2011 Apr 28
Early G₁ cyclin-dependent kinases as prognostic markers and potential therapeutic targets in esophageal adenocarcinoma.
2011 Jul 1
p16-Cdk4-Rb axis controls sensitivity to a cyclin-dependent kinase inhibitor PD0332991 in glioblastoma xenograft cells.
2012 Jul
Therapeutic response to CDK4/6 inhibition in breast cancer defined by ex vivo analyses of human tumors.
2012 Jul 15
CDK4/6 inhibition antagonizes the cytotoxic response to anthracycline therapy.
2012 Jul 15
The CDK4/6 inhibitor PD0332991 reverses epithelial dysplasia associated with abnormal activation of the cyclin-CDK-Rb pathway.
2012 Jun
Cdk4/6 inhibition induces epithelial-mesenchymal transition and enhances invasiveness in pancreatic cancer cells.
2012 Oct
Therapeutic targeting of the cyclin D3:CDK4/6 complex in T cell leukemia.
2012 Oct 16
The requirement for cyclin D function in tumor maintenance.
2012 Oct 16
Attenuation of the retinoblastoma pathway in pancreatic neuroendocrine tumors due to increased cdk4/cdk6.
2012 Sep 1
PD-0332991, a CDK4/6 inhibitor, significantly prolongs survival in a genetically engineered mouse model of brainstem glioma.
2013
PD-0332991, a potent and selective inhibitor of cyclin-dependent kinase 4/6, demonstrates inhibition of proliferation in renal cell carcinoma at nanomolar concentrations and molecular markers predict for sensitivity.
2013 Aug
Inhibition of cyclin-dependent kinase 6 suppresses cell proliferation and enhances radiation sensitivity in medulloblastoma cells.
2013 Jan
A CDK4/6 inhibitor enhances cytotoxicity of paclitaxel in lung adenocarcinoma cells harboring mutant KRAS as well as wild-type KRAS.
2013 Jul
Phase II trial of the CDK4 inhibitor PD0332991 in patients with advanced CDK4-amplified well-differentiated or dedifferentiated liposarcoma.
2013 Jun 1
Induction of prolonged early G1 arrest by CDK4/CDK6 inhibition reprograms lymphoma cells for durable PI3Kδ inhibition through PIK3IP1.
2013 Jun 15
Targeting cell cycle and hormone receptor pathways in cancer.
2013 Nov 28
MLL fusion-driven activation of CDK6 potentiates proliferation in MLL-rearranged infant ALL.
2014
[Effect of PD0332991 on biological activity of hematopoietic stem cells in mice].
2014 Feb
Synergism of cyclin-dependent kinase inhibitors with camptothecin derivatives in small cell lung cancer cell lines.
2014 Feb 17
CDK4/6 inhibition provides a potent adjunct to Her2-targeted therapies in preclinical breast cancer models.
2014 Jul
Loss of CDKN2A expression is a frequent event in primary invasive melanoma and correlates with sensitivity to the CDK4/6 inhibitor PD0332991 in melanoma cell lines.
2014 Jul
CDK4/6 and IGF1 receptor inhibitors synergize to suppress the growth of p16INK4A-deficient pancreatic cancers.
2014 Jul 15
Palbociclib: first global approval.
2015 Apr
The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study.
2015 Jan
Palbociclib Extends Survival in Advanced Breast Cancer.
2015 Jul
Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer.
2015 Jul 16
CDK 4/6 inhibitor palbociclib (PD0332991) in Rb+ advanced breast cancer: phase II activity, safety, and predictive biomarker assessment.
2015 Mar 1
Phase 2 trial of the cyclin-dependent kinase 4/6 inhibitor palbociclib in patients with retinoblastoma protein-expressing germ cell tumors.
2015 May 1
Patents

Sample Use Guides

IBRANCE capsules (Palbociclib) are taken orally with food in combination with letrozole. Recommended starting dose: 125 mg once daily taken with food for 21 days followed by 7 days off treatment
Route of Administration: Oral
Palbociclib (100 nM) significantly blocks phoshorylation of pRb (phospho-Rb) at serine 780 in sensitive human breast cancer cell lines (IC50 < 150 nM).
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:32:37 UTC 2021
Edited
by admin
on Fri Jun 25 21:32:37 UTC 2021
Record UNII
G9ZF61LE7G
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PALBOCICLIB
DASH   INN   USAN   WHO-DD  
INN   USAN  
Official Name English
PALBOCICLIB [MI]
Common Name English
6-ACETYL-8-CYCLOPENTYL-5-METHYL-2-((5-(PIPERAZIN-1-YL)PYRIDIN-2-YL)AMINO)-8H-PYRIDO(2,3-D)PYRIMIDIN-7-ONE
Systematic Name English
IBRANCE
Brand Name English
PYRIDO(2,3-D)PYRIMIDIN-7(8H)-ONE, 6-ACETYL-8-CYCLOPENTYL-5-METHYL-2-((5-(1-PIPERAZINYL)-2-PYRIDINYL)AMINO)-
Systematic Name English
6-ACETYL-8-CYCLOPENTYL-5-METHYL-2-((5-(PIPERAZIN-1-YL)PYRIDIN-2-YL)AMINO(PYRIDO(2,3-D)PYRIMIDIN-7(8H)-ONE
Common Name English
PALBOCICLIB [USAN]
Common Name English
PALBOCICLIB [JAN]
Common Name English
PD-0332991
Code English
PALBOCICLIB [INN]
Common Name English
PALBOCICLIB [WHO-DD]
Common Name English
PALBOCICLIB [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
WHO-ATC L01XE33
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
FDA ORPHAN DRUG 781420
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
NCI_THESAURUS C2185
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
NCI_THESAURUS C129825
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
NDF-RT N0000175605
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
Code System Code Type Description
FDA UNII
G9ZF61LE7G
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY
MERCK INDEX
M11849
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY
EVMPD
SUB177204
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY
NDF-RT
N0000175082
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY Kinase Inhibitors [MoA]
NCI_THESAURUS
C49176
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY
ChEMBL
CHEMBL189963
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY
NDF-RT
N0000190114
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY Cytochrome P450 3A Inhibitors [MoA]
RXCUI
1601374
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY RxNorm
PUBCHEM
5330286
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY
INN
9802
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY
WIKIPEDIA
Palbociclib
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY
LACTMED
Palbociclib
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY
CAS
571190-30-2
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY
DRUG CENTRAL
4941
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY
DRUG BANK
DB09073
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY
IUPHAR
7380
Created by admin on Fri Jun 25 21:32:37 UTC 2021 , Edited by admin on Fri Jun 25 21:32:37 UTC 2021
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> SUBSTRATE
EXCRETED UNCHANGED
URINE
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> NON-INDUCER
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
IC50
EXCRETED UNCHANGED
FECAL
TARGET -> INHIBITOR
IC50
Related Record Type Details
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
MAJOR
PLASMA
METABOLITE -> PARENT
Related Record Type Details
IMPURITY -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
log P CHEMICAL
Biological Half-life PHARMACOKINETIC
pKa CHEMICAL
pKa CHEMICAL
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

CSF/PLASMA RATIO PHARMACOKINETIC ROUTE OF ADMINISTRATION
PHARMACOKINETIC
DOSE
PHARMACOKINETIC
brain-to-plasma AUC ratios
PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC