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Details

Stereochemistry ACHIRAL
Molecular Formula C15H25N5O3
Molecular Weight 323.3907
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ROCICLOVIR

SMILES

CC(C)OCC(COC(C)C)OCN1C=NC2=C1N=C(N)N=C2

InChI

InChIKey=FBHWXSOQXQBXER-UHFFFAOYSA-N
InChI=1S/C15H25N5O3/c1-10(2)21-6-12(7-22-11(3)4)23-9-20-8-18-13-5-17-15(16)19-14(13)20/h5,8,10-12H,6-7,9H2,1-4H3,(H2,16,17,19)

HIDE SMILES / InChI

Description

Ganciclovir is a synthetic acyclic nucleoside analogue of 2'-deoxyguanosine active against cytomegalovirus. Ganciclovir has been shown to be active against cytomegalovirus (CMV) and herpes simplex virus (HSV) in humans. To achieve anti-CMV activity, ganciclovir is phosphorylated first to the monophosphate form by a CMV-encoded (UL97 gene) protein kinase homologue, then to the di- and triphosphate forms by cellular kinases. Ganciclovir triphosphate concentrations may be 100-fold greater in CMV-infected than in uninfected cells, indicating preferential phosphorylation in infected cells. Ganciclovir triphosphate, once formed, persists for days in the CMV-infected cell. Ganciclovir triphosphate is believed to inhibit viral DNA synthesis by (1) competitive inhibition of viral DNA polymerases; and (2) incorporation into viral DNA, resulting in eventual termination of viral DNA elongation. Ganciclovir is indicated for the treatment of CMV retinitis in immunocompromised patients, including patients with acquired immunodeficiency syndrome (AIDS) and for the treatment of acute herpetic keratitis.

Originator

Curator's Comment: The first synthesis of ganciclovir was reported by Julien Verheyden and John Martin at Syntex Research in California in 1980 and is marketed as sodium salt (Ganciclovir sodium) under the trade names Cytovene and Cymevene.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P08546
Gene ID: NA
Gene Symbol: UL54
Target Organism: Human cytomegalovirus (strain AD169) (HHV-5) (Human herpesvirus 5)
0.08 µM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ZIRGAN

Approved Use

ZIRGAN is a topical ophthalmic antiviral that is indicated for the treatment of acute herpetic keratitis (dendritic ulcers).

Launch Date

1995
Primary
CYTOVENE

Approved Use

CYTOVENE-IV is indicated for the treatment of CMV retinitis in immunocompromised patients, including patients with acquired immunodeficiency syndrome (AIDS). CYTOVENE-IV is also indicated for the prevention of CMV disease in transplant recipients at risk for CMV disease.

Launch Date

1994
Primary
VALCYTE

Approved Use

VALCYTE is indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS)

Launch Date

2001
Primary
VALCYTE

Approved Use

VALCYTE is indicated for the prevention of CMV disease in kidney, heart, and kidney-pancreas transplant patients at high risk

Launch Date

2001
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
4.8 mg/L
1 g 3 times / day multiple, oral
dose: 1 g
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GANCICLOVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
13.3 μg/mL
5 mg/kg single, intravenous
dose: 5 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
GANCICLOVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
35.4 mg × h/L
1 g 3 times / day multiple, oral
dose: 1 g
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GANCICLOVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
53.8 μg × h/mL
5 mg/kg single, intravenous
dose: 5 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
GANCICLOVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
5.2 h
5 mg/kg single, intravenous
dose: 5 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
GANCICLOVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
1000 mg 6 times / day multiple, oral
Highest studied dose
Dose: 1000 mg, 6 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 6 times / day
Sources:
unhealthy, 37.4
n = 19
Health Status: unhealthy
Condition: AIDS
Age Group: 37.4
Population Size: 19
Sources:
2000 mg 3 times / day multiple, oral
Highest studied dose
Dose: 2000 mg, 3 times / day
Route: oral
Route: multiple
Dose: 2000 mg, 3 times / day
Sources:
unhealthy, 38.6
n = 50
Health Status: unhealthy
Condition: CMV retinitis in HIV infection
Age Group: 38.6
Population Size: 50
Sources:
Other AEs: Neutropenia, Thrombocytopenia...
Other AEs:
Neutropenia (18%)
Thrombocytopenia (4%)
Anemia (severe, 4%)
Renal impairment (4%)
Sources:
50 mg/kg 3 times / day multiple, oral
Highest studied dose
Dose: 50 mg/kg, 3 times / day
Route: oral
Route: multiple
Dose: 50 mg/kg, 3 times / day
Sources:
unhealthy, 7.4 years (range: 0.5-16.9 years)
n = 36
Health Status: unhealthy
Condition: CMV retinitis in HIV infection
Age Group: 7.4 years (range: 0.5-16.9 years)
Population Size: 36
Sources:
Other AEs: Neutropenia...
Other AEs:
Neutropenia (22%)
Sources:
5 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 5 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 5 mg/kg, 1 times / day
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: CMV retinitis in HIV infection
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Other AEs: Fever, Infection...
Other AEs:
Fever (48%)
Infection (13%)
Chills (10%)
Sepsis (15%)
Diarrhea (44%)
Anorexia (14%)
Vomiting (13%)
Leukopenia (41%)
Anemia (25%)
Thrombocytopenia (6%)
Neuropathy (9%)
Sweating (12%)
Pruritus (5%)
Catheter infection (9%)
Catheter sepsis (8%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Neutropenia 18%
2000 mg 3 times / day multiple, oral
Highest studied dose
Dose: 2000 mg, 3 times / day
Route: oral
Route: multiple
Dose: 2000 mg, 3 times / day
Sources:
unhealthy, 38.6
n = 50
Health Status: unhealthy
Condition: CMV retinitis in HIV infection
Age Group: 38.6
Population Size: 50
Sources:
Renal impairment 4%
2000 mg 3 times / day multiple, oral
Highest studied dose
Dose: 2000 mg, 3 times / day
Route: oral
Route: multiple
Dose: 2000 mg, 3 times / day
Sources:
unhealthy, 38.6
n = 50
Health Status: unhealthy
Condition: CMV retinitis in HIV infection
Age Group: 38.6
Population Size: 50
Sources:
Thrombocytopenia 4%
2000 mg 3 times / day multiple, oral
Highest studied dose
Dose: 2000 mg, 3 times / day
Route: oral
Route: multiple
Dose: 2000 mg, 3 times / day
Sources:
unhealthy, 38.6
n = 50
Health Status: unhealthy
Condition: CMV retinitis in HIV infection
Age Group: 38.6
Population Size: 50
Sources:
Anemia severe, 4%
2000 mg 3 times / day multiple, oral
Highest studied dose
Dose: 2000 mg, 3 times / day
Route: oral
Route: multiple
Dose: 2000 mg, 3 times / day
Sources:
unhealthy, 38.6
n = 50
Health Status: unhealthy
Condition: CMV retinitis in HIV infection
Age Group: 38.6
Population Size: 50
Sources:
Neutropenia 22%
50 mg/kg 3 times / day multiple, oral
Highest studied dose
Dose: 50 mg/kg, 3 times / day
Route: oral
Route: multiple
Dose: 50 mg/kg, 3 times / day
Sources:
unhealthy, 7.4 years (range: 0.5-16.9 years)
n = 36
Health Status: unhealthy
Condition: CMV retinitis in HIV infection
Age Group: 7.4 years (range: 0.5-16.9 years)
Population Size: 36
Sources:
Chills 10%
5 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 5 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 5 mg/kg, 1 times / day
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: CMV retinitis in HIV infection
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Sweating 12%
5 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 5 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 5 mg/kg, 1 times / day
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: CMV retinitis in HIV infection
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Infection 13%
5 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 5 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 5 mg/kg, 1 times / day
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: CMV retinitis in HIV infection
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Vomiting 13%
5 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 5 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 5 mg/kg, 1 times / day
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: CMV retinitis in HIV infection
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Anorexia 14%
5 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 5 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 5 mg/kg, 1 times / day
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: CMV retinitis in HIV infection
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Sepsis 15%
5 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 5 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 5 mg/kg, 1 times / day
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: CMV retinitis in HIV infection
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Anemia 25%
5 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 5 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 5 mg/kg, 1 times / day
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: CMV retinitis in HIV infection
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Leukopenia 41%
5 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 5 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 5 mg/kg, 1 times / day
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: CMV retinitis in HIV infection
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Diarrhea 44%
5 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 5 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 5 mg/kg, 1 times / day
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: CMV retinitis in HIV infection
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Fever 48%
5 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 5 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 5 mg/kg, 1 times / day
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: CMV retinitis in HIV infection
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Pruritus 5%
5 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 5 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 5 mg/kg, 1 times / day
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: CMV retinitis in HIV infection
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Thrombocytopenia 6%
5 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 5 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 5 mg/kg, 1 times / day
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: CMV retinitis in HIV infection
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Catheter sepsis 8%
5 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 5 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 5 mg/kg, 1 times / day
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: CMV retinitis in HIV infection
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Catheter infection 9%
5 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 5 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 5 mg/kg, 1 times / day
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: CMV retinitis in HIV infection
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
Neuropathy 9%
5 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 5 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 5 mg/kg, 1 times / day
Sources:
unhealthy, adult
n = 179
Health Status: unhealthy
Condition: CMV retinitis in HIV infection
Age Group: adult
Sex: M+F
Population Size: 179
Sources:
PubMed

PubMed

TitleDatePubMed
Oral ganciclovir and pharmacokinetics of valganciclovir in liver transplant recipients.
1999
Prophylaxis against herpesvirus infections in transplant recipients.
2001
Recent advances in imaging endogenous or transferred gene expression utilizing radionuclide technologies in living subjects: applications to breast cancer.
2001
Suicide gene therapy for human oral squamous cell carcinoma cell lines with adeno-associated virus vector.
2001 Apr
Intravitreal pharmacokinetics and retinal concentrations of ganciclovir and foscarnet after intravitreal administration in rabbits.
2001 Apr
Cytological monitoring of peripheral blood, bronchoalveolar lavage fluid, and transbronchial biopsy specimens during acute rejection and cytomegalovirus infection in lung and heart--lung allograft recipients.
2001 Apr
Suspension of anticytomegalovirus maintenance therapy following immune recovery due to highly active antiretroviral therapy.
2001 Apr
Risk for cytomegalovirus disease in patients receiving polymerase chain reaction-based preemptive antiviral therapy after allogeneic stem cell transplantation depends on transplantation modality.
2001 Apr 1
Protection from lethal murine graft-versus-host disease without compromise of alloengraftment using transgenic donor T cells expressing a thymidine kinase suicide gene.
2001 Apr 15
A time to live, a time to die.
2001 Apr 15
Adenoviral-mediated gene therapy for thyroid carcinoma using thymidine kinase controlled by thyroglobulin promoter demonstrates high specificity and low toxicity.
2001 Feb
[Cytomegalovirus rhombencephalomyelitis in an immunocompetent subject].
2001 Feb
Gamma-rays enhance rAAV-mediated transgene expression and cytocidal effect of AAV-HSVtk/ganciclovir on cancer cells.
2001 Feb
Human prostate carcinoma cells as targets for herpes simplex virus thymidine kinase-mediated suicide gene therapy.
2001 Feb
Immune-dependent distant bystander effect after adenovirus-mediated suicide gene transfer in a rat model of liver colorectal metastasis.
2001 Feb
Effect of the complexation with cyclodextrins on the in vitro antiviral activity of ganciclovir against human cytomegalovirus.
2001 Feb
Genetic risks of antiviral nucleoside analogues--a survey.
2001 Feb
Conditional abatement of tissue fibrosis using nucleoside analogs to selectively corrupt DNA replication in transgenic fibroblasts.
2001 Feb
Failure of cidofovir to reduce CMV-antigenemia in a child transplanted from a matched unrelated donor.
2001 Feb
Stimulation of intercellular communication of poor-communicating cells by gap-junction-competent cells enhances the HSV-TK/GCV bystander effect in vitro.
2001 Feb 15
Ovarian epithelial cell lineage-specific gene expression using the promoter of a retrovirus-like element.
2001 Feb 15
Coexpression of the partial androgen receptor enhances the efficacy of prostate-specific antigen promoter-driven suicide gene therapy for prostate cancer cells at low testosterone concentrations.
2001 Feb 15
A tightly regulated immortalized human fetal hepatocyte cell line to develop a bioartificial liver.
2001 Feb-Mar
Meta-analysis of prophylaxis of CMV disease in solid organ transplantation: is Ganciclovir a superior agent to Acyclovir?
2001 Feb-Mar
Preemptive ganciclovir for CMV viremia in liver transplantation.
2001 Feb-Mar
Prophylactic antiviral therapy in CMV high-risk liver transplant recipients.
2001 Feb-Mar
Is preemptive therapy for CMV infection following liver transplantation superior to symptom-triggered treatment?
2001 Feb-Mar
Cytomegalovirus infection-enhanced chronic rejection in the rat is prevented by antiviral prophylaxis.
2001 Feb-Mar
Ganciclovir prophylaxis for cytomegalovirus infection in simultaneous kidney-pancreas transplant recipients receiving tacrolimus, mycophenolate mofetil, and prednisone.
2001 Feb-Mar
CMV in kidney transplants in the tacrolimus-mycophenolate era.
2001 Feb-Mar
Rat glioma cell death induced by cationic liposome-mediated transfer of the herpes simplex virus thymidine kinase gene followed by ganciclovir treatment.
2001 Jan
Targeting the replication of adenovirus to p53-defective thyroid carcinoma with a p53-regulated Cre/loxP system.
2001 Jan
Toxic megacolon: remember cytomegalovirus.
2001 Mar
Cytomegalovirus colitis complicating ulcerative colitis in the steroid-naive patient.
2001 Mar
Prevalence of cytomegalovirus infection in severe refractory ulcerative and Crohn's colitis.
2001 Mar
Characterization of the cyclooxygenase-2 promoter in an adenoviral vector and its application for the mitigation of toxicity in suicide gene therapy of gastrointestinal cancers.
2001 Mar
The real danger of lamivudine-resistant hepatitis B virus infection in the immunocompromised host.
2001 Mar
High-dose intravitreal ganciclovir and foscarnet for cytomegalovirus retinitis.
2001 Mar
Frosted branch angiitis in a child with HIV infection.
2001 Mar
New developments in the management of cytomegalovirus infection and disease after renal transplantation.
2001 Mar
Protease pretreatment increases the efficacy of adenovirus-mediated gene therapy for the treatment of an experimental glioblastoma model.
2001 Mar 1
Expression of herpes simplex virus-thymidine kinase gene controlled by a promoter region of the midkine gene confers selective cytotoxicity to ganciclovir in human carcinoma cells.
2001 Mar 1
Preevaluation of clinical trial data: the case of preemptive cytomegalovirus therapy in patients with human immunodeficiency virus.
2001 Mar 1
Preemptive therapy versus universal prophylaxis with ganciclovir for cytomegalovirus in solid organ transplant recipients.
2001 Mar 1
Adenovirus-mediated gene therapy specific for small cell lung cancer cells using a Myc-Max binding motif.
2001 Mar 15
Prophylaxis for CMV should not now replace pre-emptive therapy in solid organ transplantation.
2001 Mar-Apr
Reactivity of valganciclovir in aqueous solution.
2005 Oct
The Role of Antiviral Prophylaxis for the Prevention of Epstein-Barr Virus-Associated Posttransplant Lymphoproliferative Disease in Solid Organ Transplant Recipients: A Systematic Review.
2017 Mar
A 42-Year-Old Woman With Anemia, Shock, and Ischemic Stroke After Lung Transplantation.
2017 Mar
Top 1% of Inpatients Administered Antimicrobial Agents Comprising 50% of Expenditures: A Descriptive Study and Opportunities for Stewardship Intervention.
2017 Mar
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: Ganciclovir can be used as ophthalmic gel 1 drop in the affected eye 5 times per day in patients with acute herpetic keratitis.
Unknown
Route of Administration: Unknown
In Vitro Use Guide
Curator's Comment: The median concentration of ganciclovir that inhibits CMV replication (IC50) in vitro (laboratory strains or clinical isolates) has ranged from 0.02 to 3.48 ug/mL.
Unknown
Name Type Language
ROCICLOVIR
INN  
INN  
Official Name English
HOE-602
Code English
rociclovir [INN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1556
Created by admin on Sat Dec 16 16:48:28 GMT 2023 , Edited by admin on Sat Dec 16 16:48:28 GMT 2023
NCI_THESAURUS C29575
Created by admin on Sat Dec 16 16:48:28 GMT 2023 , Edited by admin on Sat Dec 16 16:48:28 GMT 2023
NCI_THESAURUS C281
Created by admin on Sat Dec 16 16:48:28 GMT 2023 , Edited by admin on Sat Dec 16 16:48:28 GMT 2023
Code System Code Type Description
PUBCHEM
65905
Created by admin on Sat Dec 16 16:48:28 GMT 2023 , Edited by admin on Sat Dec 16 16:48:28 GMT 2023
PRIMARY
EVMPD
SUB10351MIG
Created by admin on Sat Dec 16 16:48:28 GMT 2023 , Edited by admin on Sat Dec 16 16:48:28 GMT 2023
PRIMARY
NCI_THESAURUS
C73204
Created by admin on Sat Dec 16 16:48:28 GMT 2023 , Edited by admin on Sat Dec 16 16:48:28 GMT 2023
PRIMARY
INN
6503
Created by admin on Sat Dec 16 16:48:28 GMT 2023 , Edited by admin on Sat Dec 16 16:48:28 GMT 2023
PRIMARY
CAS
108436-80-2
Created by admin on Sat Dec 16 16:48:28 GMT 2023 , Edited by admin on Sat Dec 16 16:48:28 GMT 2023
PRIMARY
EPA CompTox
DTXSID10148548
Created by admin on Sat Dec 16 16:48:28 GMT 2023 , Edited by admin on Sat Dec 16 16:48:28 GMT 2023
PRIMARY
ChEMBL
CHEMBL111232
Created by admin on Sat Dec 16 16:48:28 GMT 2023 , Edited by admin on Sat Dec 16 16:48:28 GMT 2023
PRIMARY
SMS_ID
100000080268
Created by admin on Sat Dec 16 16:48:28 GMT 2023 , Edited by admin on Sat Dec 16 16:48:28 GMT 2023
PRIMARY
FDA UNII
6DF29U51Y7
Created by admin on Sat Dec 16 16:48:28 GMT 2023 , Edited by admin on Sat Dec 16 16:48:28 GMT 2023
PRIMARY