Structura chimica Denumirea Denumiri sinonime ale

uzuala a medicamentului (drug name

medicamentului synonyms)
(drug common
name)
Rosuvastatin ZD-4522, rosuvastatin calcium,
Astende, Cirantan, Cresadex,
Crestor, Provisacor, Razel,
Rosedex, Rosimol, Rosumed,
Rosustatin, Rosuvas, Rosuvast,
Rosvel, Rovartal, Simestat, Sinlip,
Visacor, Vivacor

Metabolititi pharmGKB ID
(metabolites)
n-desmethyl rosuvastatin, PA134308647
rosuvastatin lactone

Tabel.1 informatia generala despre medicament

Pharm GKB ID al Sursa Sumarul recomandarii

aplicarii recomandarii
PA166184427 Swissmedic label for The Swiss drug label for ezetimibe/rosuvastatin
Rosuvastatin und (Ezetimib-Rosuvastatin-Mepha Kapseln) states
Ezetimib. that genetic polymorphisms in SLCO1B1 and
ABCG2 may lead to an increase in rosuvastatin
exposure, a reduction in the dosage is
recommended.

PA166184499 Swissmedic label for The Swiss drug label for rosuvastatin (Crestor)
rosuvastatin. states that genetic polymorphisms in SLCO1B1
and ABCG2 may lead to an increase in
rosuvastatin exposure, a reduction in the dosage
is recommended.
Tabel 2. Recomandarile clinice referitor la prescrierea medicamentului
Sursa Genele
U.S. Food and Drug Administration SLCO1B1
Health Canada Santé Canada LDLR
Swissmedic ABCG2, SLCO1B1
Swissmedic ABCG2, SLCO1B1
Tabel 3. Adnotarea marcii medicamentului

Variant Gene Type Phenotype

rs20455 KIF6 Efficacy Hypercholesterolemia

SLCO1B1*15 SLCO1B1
SLCO1B1*18
Metabolism/PK
SLCO1B1*1A
SLCO1B1*1B
SLCO1B1*5 SLCO1B1*9
rs1205 CRP efficacy Coronary disease

rs2199939 ABCG2 efficacy

rs4149081 SLCO1B1 efficacy Coronary disease

rs6535454 COQ2 Toxicity/ADR Muscular disease

HLA-DRB1*01:01:01 HLA-DRB1 Toxicity/ADR
HLA-DRB1*04:06:01

rs2808630 efficacy Coronary disease

rs776746 CYP3A5 efficacy Myocardial Infarction

rs2231142 ABCG2 efficacy Hypercholesterolemia

Myocardial Infarction
rs4693075 COQ2 Toxicity/ADR Muscular Diseases

rs1736557 FMO3 efficacy

rs4149056 SLCO1B1 other Hypercholesterolemia

rs2231142 ABCG Metabolism/PK

rs4149056 SLCO1B1 Toxicity/ADR Coronary Artery
Disease statin-
related myopathy

Tabel 4. Adnotarea clinica

variant gene significant P Study Biogeographical Paper PMID
value size group discusse

rs10455872 LPA yes =3.5e- 6989 european efficacy 22331829

9

association Genotypes AG + GG are associated with decreased response to rosuvastatin as

compared to genotype AA.

rs7412 APOE no - 73 european efficacy 17289397

association Genotype CT is associated with increased likelihood of lipid response when treated with
atorvastatin, fluvastatin, pravastatin, rosuvastatin or simvastatin as compared to
genotype CC.

rs4693075 COQ2 yes <3.0E- 76 european toxicity 20347093

4
association Allele G is associated with increased risk of Muscular Diseases when treated with
atorvastatin or rosuvastatin in people with Hyperlipoproteinemia Type II as compared
to allele C.

CYP2C*2 CYP2C9 no - 32 european toxicity 17289397

association CYP2C9 *2 is not associated with likelihood of myopathy when treated with fluvastatin,
rosuvastatin or simvastatin as compared to CYP2C9 *1.

CYP2C9*3 CYP2C9 no - 32 european toxicity 17289397

association CYP2C9 *3 is not associated with likelihood of myopathy when treated with fluvastatin,
rosuvastatin or simvastatin as compared to CYP2C9 *1.
rs768445692 CACNA1S no - 1 european toxicity 30325262

association Allele C is associated with Rhabdomyolysis and statin-related myopathy when treated
with rosuvastatin as compared to allele T.
rs9806699 GATM no =0.83 3052 european toxicity 23995691

association Allele A is not associated with increased creatine kinase level when treated with hmg
coa reductase inhibitors, rosuvastatin or simvastatin as compared to allele G.
CYP2C9*1 CYP2C9 no - 32 european efficacy 17289397

CYP2C9*3

association CYP2C9 *1/*3 is not associated with lipid response when treated with fluvastatin,
rosuvastatin or simvastatin as compared to CYP2C9 *1/*1.
rs2306283 SLCO1B1 yes = 36 european Metabolism/ 16198652
0.0456 PK

association Genotype GG is associated with increased concentrations of rosuvastatin in healthy

individuals as compared to genotype AA.
rs17238540 HMGCR yes = 5.0E- 1061 european efficacy 18815589
4

association Genotype GT is associated with decreased likelihood of reaching target cholesterol

 levels when treated with atorvastatin, cerivastatin, fluvastatin, pravastatin, rosuvastatin
or simvastatin in people with Diabetes Mellitus as compared to genotype TT.

rs12487736 SCAP yes = 0.001 142 european efficacy 29318930

association Allele C is associated with increased response to rosuvastatin in people with Metabolic
Syndrome as compared to allele T.

rs1481012 ABCG2 yes = 1.7e- 6989 european efficacy 22331829

15
associaion Genotypes AG + GG are associated with increased response to rosuvastatin as
compared to genotype AA.

rs17111584 USP24 yes =5.8e-4 6989 european efficacy 22331829

association Genotypes CC + CT are associated with decreased response to rosuvastatin as
compared to genotype TT.

rs71352238 APOE yes =2.9e 4 6989 european efficacy 22331829

association Genotypes CC + CT are associated with decreased response to rosuvastatin as
compared to genotype TT.

Tabel 5. Descrierea variantelor

Img.1 Procese metabolice

Database category Database name Database description Number of records

Literature Bookshelf A collection of 472
biomedical books that
can be searched
directly or from
linked data in other
NCBI databases. The
collection includes
biomedical textbooks,
other scientific titles,
genetic resources
such as GeneReviews,
and NCBI help
manuals.

MeSH MeSH (Medical 3

Subject Headings) is
the U.S. National
Library of Medicine's
controlled vocabulary
for indexing articles
for
MEDLINE/PubMed.
MeSH terminology
provides a consistent
way to retrieve
information that may
use different
terminology for the
same concepts.
Bibliographic data for
all the journals,
NLM Catalog 1
books, audiovisuals,
computer software,
electronic resources
and other materials
that are in the
library's holdings.

PubMed A database of 3,962

citations and
abstracts for
biomedical literature
from MEDLINE and
additional life science
journals. Links are
provided when full
text versions of the
articles are available
 via PubMed Central
(described below) or
other websites.

PubMed Central A digital archive of 11,740

full-text biomedical
and life sciences
journal literature,
including clinical
medicine and public
health.
Genes Gene A searchable 87
database of genes,
focusing on genomes
that have been
completely
sequenced and that
have an active
research community
to contribute gene-
specific data.
Information includes
nomenclature,
chromosomal
localization, gene
products and their
attributes (e.g.,
protein interactions),
associated markers,
phenotypes,
interactions, and links
to citations,
sequences, variation
details, maps,
expression reports,
homologs, protein
domain content, and
external databases.

GEO DataSets Stores curated gene 487

expression and
molecular abundance
DataSets assembled
from the Gene
Expression Omnibus
(GEO) repository.
DataSet records
contain additional
resources, including
cluster tools and
 differential
expression queries.

GEO Profiles Stores individual gene 0

expression and
molecular abundance
Profiles assembled
from the Gene
Expression Omnibus
(GEO) repository.
Search for specific
profiles of interest
based on gene
annotation or pre-
computed profile
characteristics.
PopSet Database of related 0
DNA sequences that
originate from
comparative studies:
phylogenetic,
population,
environmental and,
to a lesser degree,
mutational. Each
record in the
database is a set of
DNA sequences. For
example, a
population set
provides information
on genetic variation
within an organism,
while a phylogenetic
set may contain
sequences, and their
alignment, of a single
gene obtained from
several related
organisms.

Proteins Conserved Domains A collection of 0

sequence alignments
and profiles
representing protein
domains conserved in
molecular evolution.
It also includes
alignments of the
domains to known 3-
 dimensional protein
structures in the
MMDB database.

Identical Protein A collection of 0

Groups consolidated records
describing proteins
identified in
annotated coding
regions in GenBank
and RefSeq, as well as
SwissProt and PDB
protein sequences.
This resource allows
investigators to
obtain more targeted
search results and
quickly identify a
protein of interest.
Protein A database that 33
includes protein
sequence records
from a variety of
sources, including
GenPept, RefSeq,
Swiss-Prot, PIR, PRF,
and PDB.

Protein clusters A collection of related 0

protein sequences
(clusters), consisting
of Reference
Sequence proteins
encoded by complete
prokaryotic and
organelle plasmids
and genomes. The
database provides
easy access to
annotation
information,
publications,
domains, structures,
external links, and
analysis tools.
Structure Contains 2
macromolecular 3D
structures derived
from the Protein Data
 Bank, as well as tools
for their visualization
and comparative
analysis.

Genomes Assembly A database providing 0

information on the
structure of
assembled genomes,
assembly names and
other meta-data,
statistical reports,
and links to genomic
sequence data.
BioCollections A curated set of 0
metadata for culture
collections, museums,
herbaria and other
natural history
collections. The
records display
collection codes,
information about
the collections' home
institutions, and links
to relevant data at
NCBI.

BioProject A collection of 12
genomics, functional
genomics, and
genetics studies and
links to their resulting
datasets. This
resource describes
project scope,
material, and
objectives and
provides a
mechanism to
retrieve datasets that
are often difficult to
find due to
inconsistent
annotation, multiple
independent
submissions, and the
varied nature of
diverse data types
which are often
 stored in different
databases.

BioSample The BioSample 92

database contains
descriptions of
biological source
materials used in
experimental assays.
Genome Contains sequence 0
and map data from
the whole genomes
of over 1000
organisms. The
genomes represent
both completely
sequenced organisms
and those for which
sequencing is in
progress. All three
main domains of life
(bacteria, archaea,
and eukaryota) are
represented, as well
as many viruses,
phages, viroids,
plasmids, and
organelles.

Nucleotide A collection of 43
nucleotide sequences
from several sources,
including GenBank,
RefSeq, the Third
Party Annotation
(TPA) database, and
PDB. Searching the
Nucleotide Database
will yield available
results from each of
its component
databases.
SRA The Sequence Read 86
Archive (SRA) stores
sequencing data from
the next generation
of sequencing
platforms including
Roche 454 GS
System®, Illumina
 Genome Analyzer®,
Life Technologies AB
SOLiD System®,
Helicos Biosciences
Heliscope®, Complete
Genomics®, and
Pacific Biosciences
SMRT®.

Taxonomy Contains the names 0

and phylogenetic
lineages of more than
160,000 organisms
that have molecular
data in the NCBI
databases. New taxa
are added to the
Taxonomy database
as data are deposited
for them.
Clinical [Link] A registry and results 644
database of publicly-
and privately-
supported clinical
studies of human
participants
conducted around the
world.

ClinVar A resource to provide 3

a public, tracked
record of reported
relationships
between human
variation and
observed health
status with
supporting evidence.
Related information
in the NIH Genetic
Testing Registry
(GTR), MedGen,
Gene, OMIM,
PubMed and other
sources is accessible
through hyperlinks on
the records.
dbGaP An archive and 7
distribution center for
the description and
 results of studies
which investigate the
interaction of
genotype and
phenotype. These
studies include
genome-wide
association (GWAS),
medical
resequencing,
molecular diagnostic
assays, as well as
association between
genotype and non-
clinical traits.

dbSNP Includes single 0

nucleotide variations,
microsatellites, and
small-scale insertions
and deletions. dbSNP
contains population-
specific frequency
and genotype data,
experimental
conditions, molecular
context, and mapping
information for both
neutral variations and
clinical mutations.
dbVar The dbVar database 0
has been developed
to archive
information
associated with large
scale genomic
variation, including
large insertions,
deletions,
translocations and
inversions. In addition
to archiving variation
discovery, dbVar also
stores associations of
defined variants with
phenotype
information.

GTR A voluntary registry of 3

genetic tests and
 laboratories, with
detailed information
about the tests such
as what is measured
and analytic and
clinical validity. GTR
also is a nexus for
information about
genetic conditions and
provides context-
specific links to a
variety of resources,
including practice
guidelines, published
literature, and genetic
data/information. The
initial scope of GTR
includes single gene
tests for Mendelian
disorders, as well as
arrays, panels and
pharmacogenetic
tests.

MedGen A portal to 11
information about
medical genetics.
MedGen includes
term lists from
multiple sources and
organizes them into
concept groupings and
hierarchies. Links are
also provided to
information related to
those concepts in the
NIH Genetic Testing
Registry (GTR),
ClinVar, Gene, OMIM,
PubMed, and other
sources.
OMIM A database of human 1
genes and genetic
disorders. NCBI
maintains current
content and continues
to support its
searching and
integration with other
NCBI databases.
 However, OMIM now
has a new home at
[Link], and users
are directed to this
site for full record
displays.

PubChem BioAssays Consists of deposited 114

bioactivity data and
descriptions of
bioactivity assays
used to screen the
chemical substances
contained in the
PubChem Substance
database, including
descriptions of the
conditions and the
readouts (bioactivity
levels) specific to the
screening procedure.
Compounds Contains unique, 84
validated chemical
structures (small
molecules) that can be
searched using names,
synonyms or
keywords. The
compound records
may link to more than
one PubChem
Substance record if
different depositors
supplied the same
structure. These
Compound records
reflect validated
chemical depiction
information provided
to describe substances
in PubChem
Substance. Structures
stored within
PubChem Compounds
are pre-clustered and
cross-referenced by
identity and similarity
groups. Additionally,
calculated properties
and descriptors are
 available for searching
and filtering of
chemical structures.

Substances PubChem Substance 576

records contain
substance information
electronically
submitted to
PubChem by
depositors. This
includes any chemical
structure information
submitted, as well as
chemical names,
comments, and links
to the depositor's web
site.
Tabel 6. Rezultatele cautarii in NCBI

Numarul total de articole 1436

Numarul de articole in
ultimul an

1. Zheng Zequn, W.U. Yujia, Q.I.A.N. Dingding, L.I.A.N. Jiangfang. Off-label use of chloroquine,
hydroxychloroquine, azithromycin and lopinavir/ritonavir in COVID-19 risks prolonging the QT
interval by targeting the hERG channel. Eur J Pharmacol. 2020 Dec 18 : 173813. doi:
10.1016/[Link].2020.173813. PMCID: PMC7746509

2. Mengyuan Liang, Miao He, Jian Tang, Xinliang He, Zhijun Liu, Siwei Feng, Ping Chen, Hui Li, Yu’e
Xue, Tao Bai, Yanling Ma, Jianchu Zhang. Novel risk scoring system for predicting acute respiratory
distress syndrome among hospitalized patients with coronavirus disease 2019 in Wuhan, China.
BMC Infect Dis. 2020; 20: 960. Published online 2020 Dec 17. doi: 10.1186/s12879-020-05561-y.
PMCID: PMC7744733
3. Neus Gimenez, Rupal Tripathi, Ariadna Giró, Laia Rosich, Mònica López-Guerra, Irene López-
Oreja, Heribert Playa-Albinyana, Fabian Arenas, José Manuel Mas, Patricia Pérez-Galán, Julio
Delgado, Elias Campo, Judith Farrés, Dolors Colomer. Systems biology drug screening identifies
statins as enhancers of current therapies in chronic lymphocytic leukemia. Sci Rep. 2020; 10:
22153. Published online 2020 Dec 17. doi: 10.1038/s41598-020-78315-0. PMCID: PMC7746765

4. Sean DeAngelo, Kailyn I. Mann, Muhammad Abdulbasit, Amy Ahnert, Deborah W. Sundlöf. A
case report: rapid progression of coronary atherosclerosis in a patient taking Targretin
(Bexarotene). Cardiooncology. 2020; 6: 31. Published online 2020 Dec 14. doi: 10.1186/s40959-020-
00087-3. PMCID: PMC7734706
5. Pratibha Singh, Isabel Goncalves, Christoffer Tengryd, Mihaela Nitulescu, Ana F. Persson, Fong
To, Eva Bengtsson, Petr Volkov, Marju Orho-Melander, Jan Nilsson, Andreas Edsfeldt. Reduced
oxidized LDL in T2D plaques is associated with a greater statin usage but not with future
cardiovascular events. Cardiovasc Diabetol. 2020; 19: 214. Published online 2020 Dec 14. doi:
10.1186/s12933-020-01189-z. PMCID: PMC7737372

6. Júlia Karády, Thomas Mayrhofer, Alexander Ivanov, Borek Foldyna, Michael T. Lu, Maros
Ferencik, Amit Pursnani, Michael Salerno, James E. Udelson, Daniel B. Mark, Pamela S. Douglas,
Udo Hoffmann. Cost-effectiveness Analysis of Anatomic vs Functional Index Testing in Patients
With Low-Risk Stable Chest Pain. JAMA Netw Open. 2020 Dec; 3(12): e2028312. Published online
2020 Dec 14. doi: 10.1001/jamanetworkopen.2020.28312. PMCID: PMC7737090
7. Dietmar Urbach, Friedemann Awiszus, Sven Leiß, Tamsin Venton, Alexander Vincent De Specht,
Christian Apfelbacher. Associations of Medications With Lower Odds of Typical COVID-19
Symptoms: Cross-Sectional Symptom Surveillance Study. JMIR Public Health Surveill. 2020 Oct-Dec;
6(4): e22521. Published online 2020 Dec 14. doi: 10.2196/22521. PMCID: PMC7744147

8. Peng-Fei Zheng, Rui-Xing Yin, Yao-Zong Guan, Bi-Liu Wei, Chun-Xiao Liu, Guo-Xiong Deng.
Association between SLC44A4-NOTCH4 SNPs and serum lipid levels in the Chinese Han and
Maonan ethnic groups. Nutr Metab (Lond) 2020; 17: 105. Published online 2020 Dec 14. doi:
10.1186/s12986-020-00533-0. PMCID: PMC7737288
9. Yi-Heng Li, Wei-Kung Tseng, Wei-Hsian Yin, Fang-Ju Lin, Yen-Wen Wu, I-Chang Hsieh, Tsung-
Hsien Lin, Wayne Huey-Herng Sheu, Hung-I Yeh, Jaw-Wen Chen, Chau-Chung Wu, Taiwanese
Secondary Prevention for Patients with AtheRosCLErotic Disease (T-SPARCLE) Registry
Investigators. Prognostic effect of high-density lipoprotein cholesterol level in patients with
atherosclerotic cardiovascular disease under statin treatment. Sci Rep. 2020; 10: 21835. Published
online 2020 Dec 14. doi: 10.1038/s41598-020-78828-8. PMCID: PMC7736267

10. Reactions Weekly. Multiple drugs: Delirium following off-label use and sedation: 10 case
reports. 2020; 1834(1): 176–177. Published online 2020 Dec 12. doi: 10.1007/s40278-020-87368-1.
PMCID: PMC7728506
Tabel 7. Publicatiile referitor la medicament

Pusca Corina, grM1625