Details
Stereochemistry | EPIMERIC |
Molecular Formula | C14H22N6O5 |
Molecular Weight | 354.3617 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 2 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)[C@H](N)C(=O)OCC(CO)OCN1C=NC2=C1N=C(N)NC2=O
InChI
InChIKey=WPVFJKSGQUFQAP-GKAPJAKFSA-N
InChI=1S/C14H22N6O5/c1-7(2)9(15)13(23)24-4-8(3-21)25-6-20-5-17-10-11(20)18-14(16)19-12(10)22/h5,7-9,21H,3-4,6,15H2,1-2H3,(H3,16,18,19,22)/t8?,9-/m0/s1
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/2177317 | https://www.ncbi.nlm.nih.gov/pubmed/3265058 | https://adisinsight.springer.com/drugs/800001059https://www.ncbi.nlm.nih.gov/pubmed/16305999http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021304s008,022257s003lbl.pdfhttp://www.accessdata.fda.gov/drugsatfda_docs/label/2006/019661s030lbl.pdfCurator's Comment: description was created based on several sources, including:
https://www.drugs.com/monograph/valganciclovir-hydrochloride.html | http://www.rxlist.com/valcyte-drug/indications-dosage.htm
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2177317 | https://www.ncbi.nlm.nih.gov/pubmed/3265058 | https://adisinsight.springer.com/drugs/800001059https://www.ncbi.nlm.nih.gov/pubmed/16305999http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021304s008,022257s003lbl.pdfhttp://www.accessdata.fda.gov/drugsatfda_docs/label/2006/019661s030lbl.pdf
Curator's Comment: description was created based on several sources, including:
https://www.drugs.com/monograph/valganciclovir-hydrochloride.html | http://www.rxlist.com/valcyte-drug/indications-dosage.htm
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
Sources: https://worldwide.espacenet.com/publicationDetails/biblio?II=0&ND=3&adjacent=true&locale=en_EP&FT=D&date=19960131&CC=EP&NR=0694547A2&KC=A2http://shodhganga.inflibnet.ac.in/bitstream/10603/2450/15/15_chapter%204.pdf
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
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: P08546 Gene ID: NA Gene Symbol: UL54 Target Organism: Human cytomegalovirus (strain AD169) (HHV-5) (Human herpesvirus 5) |
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Target ID: CHEMBL3414 |
0.08 µM [EC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | ZIRGAN Approved UseZIRGAN is a topical ophthalmic antiviral that is indicated for the treatment of acute herpetic keratitis (dendritic ulcers). Launch Date1995 |
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Primary | CYTOVENE Approved UseCYTOVENE-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 Date1994 |
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Primary | VALCYTE Approved UseVALCYTE is indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS) Launch Date2001 |
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Primary | VALCYTE Approved UseVALCYTE is indicated for the prevention of CMV disease in kidney, heart, and kidney-pancreas transplant patients at high risk Launch Date2001 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
4.8 mg/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/10747829 |
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 EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16737936 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
35.4 mg × h/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/10747829 |
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 EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16737936 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5.2 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16737936 |
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
Dose | Population | Adverse 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 |
|
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 |
Other AEs: Neutropenia, Thrombocytopenia... Other AEs: Neutropenia (18%) Sources: Thrombocytopenia (4%) Anemia (severe, 4%) Renal impairment (4%) |
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) Health Status: unhealthy Age Group: 7.4 years (range: 0.5-16.9 years) Sources: |
Other AEs: Neutropenia... |
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 Health Status: unhealthy Age Group: adult Sex: M+F Sources: |
Other AEs: Fever, Infection... Other AEs: Fever (48%) Sources: 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%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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 |
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 |
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 |
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 |
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) Health Status: unhealthy Age Group: 7.4 years (range: 0.5-16.9 years) 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 Health Status: unhealthy Age Group: adult Sex: M+F 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 Health Status: unhealthy Age Group: adult Sex: M+F 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 Health Status: unhealthy Age Group: adult Sex: M+F 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 Health Status: unhealthy Age Group: adult Sex: M+F 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 Health Status: unhealthy Age Group: adult Sex: M+F 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 Health Status: unhealthy Age Group: adult Sex: M+F 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 Health Status: unhealthy Age Group: adult Sex: M+F 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 Health Status: unhealthy Age Group: adult Sex: M+F 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 Health Status: unhealthy Age Group: adult Sex: M+F 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 Health Status: unhealthy Age Group: adult Sex: M+F 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 Health Status: unhealthy Age Group: adult Sex: M+F 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 Health Status: unhealthy Age Group: adult Sex: M+F 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 Health Status: unhealthy Age Group: adult Sex: M+F 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 Health Status: unhealthy Age Group: adult Sex: M+F 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 Health Status: unhealthy Age Group: adult Sex: M+F Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/22777050/ |
PubMed
Title | Date | PubMed |
---|---|---|
Guanosine analogues as anti-herpesvirus agents. | 2000 Oct-Dec |
|
Prophylaxis against herpesvirus infections in transplant recipients. | 2001 |
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Recent advances in imaging endogenous or transferred gene expression utilizing radionuclide technologies in living subjects: applications to breast cancer. | 2001 |
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Pharmacokinetics of the ganciclovir implant in the silicone-filled eye. | 2001 |
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Intravitreal pharmacokinetics and retinal concentrations of ganciclovir and foscarnet after intravitreal administration in rabbits. | 2001 Apr |
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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 |
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Suspension of anticytomegalovirus maintenance therapy following immune recovery due to highly active antiretroviral therapy. | 2001 Apr |
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Gamma-rays enhance rAAV-mediated transgene expression and cytocidal effect of AAV-HSVtk/ganciclovir on cancer cells. | 2001 Feb |
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Human prostate carcinoma cells as targets for herpes simplex virus thymidine kinase-mediated suicide gene therapy. | 2001 Feb |
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Immune-dependent distant bystander effect after adenovirus-mediated suicide gene transfer in a rat model of liver colorectal metastasis. | 2001 Feb |
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Effect of the complexation with cyclodextrins on the in vitro antiviral activity of ganciclovir against human cytomegalovirus. | 2001 Feb |
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Genetic risks of antiviral nucleoside analogues--a survey. | 2001 Feb |
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Coexistent cutaneous Aspergillus and cytomegalovirus infection in a liver transplant recipient. | 2001 Feb |
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Rhodococcus equi and cytomegalovirus pneumonia in a renal transplant patient: diagnosis by fine-needle aspiration biopsy. | 2001 Feb |
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Mutation of Gln125 to Asn selectively abolishes the thymidylate kinase activity of herpes simplex virus type 1 thymidine kinase. | 2001 Feb |
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Construction of gene therapy vectors targeting thyroid cells: enhancement of activity and specificity with histone deacetylase inhibitors and agents modulating the cyclic adenosine 3',5'-monophosphate pathway and demonstration of activity in follicular and anaplastic thyroid carcinoma cells. | 2001 Feb |
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Selective killing of human immunodeficiency virus-infected cells by targeted gene transfer and inducible gene expression using a recombinant human immunodeficiency virus vector. | 2001 Feb 10 |
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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 |
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Ovarian epithelial cell lineage-specific gene expression using the promoter of a retrovirus-like element. | 2001 Feb 15 |
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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 |
|
Rising pp65 antigenemia during preemptive anticytomegalovirus therapy after allogeneic hematopoietic stem cell transplantation: risk factors, correlation with DNA load, and outcomes. | 2001 Feb 15 |
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A tightly regulated immortalized human fetal hepatocyte cell line to develop a bioartificial liver. | 2001 Feb-Mar |
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Meta-analysis of prophylaxis of CMV disease in solid organ transplantation: is Ganciclovir a superior agent to Acyclovir? | 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 |
|
CMV in kidney transplants in the tacrolimus-mycophenolate era. | 2001 Feb-Mar |
|
Recurrent disseminated herpes zoster and cytomegalic perianal ulcer: a case report and review of the literature. | 2001 Jan |
|
Imaging in vivo herpes simplex virus thymidine kinase gene transfer to tumour-bearing rodents using positron emission tomography and. | 2001 Jan |
|
[Perspectives on postgenome medicine: Gene therapy for brain tumors]. | 2001 Jan |
|
In vitro effects of antiviral agents on human keratocytes. | 2001 Jan |
|
Management of complications associated with totally implantable ports in patients with AIDS. | 2001 Jan |
|
Cytomegalovirus hemorrhagic gastritis. | 2001 Jan |
|
Cytomegalovirus infection and non-neutropenic fever after autologous stem cell transplantation: high rates of reactivation in patients with multiple myeloma and lymphoma. | 2001 Jan |
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Isolation and analysis of an aciclovir-resistant murine cytomegalovirus mutant. | 2001 Jan |
|
Gene therapy for hepatocellular carcinoma based on tumour-selective suicide gene expression using the alpha-fetoprotein (AFP) enhancer and a housekeeping gene promoter. | 2001 Jan |
|
Retinal detachment risk in cytomegalovirus retinitis related to the acquired immunodeficiency syndrome. | 2001 Jan |
|
Retrovector encoding a green fluorescent protein-herpes simplex virus thymidine kinase fusion protein serves as a versatile suicide/reporter for cell and gene therapy applications. | 2001 Jan 1 |
|
Disseminated cytomegalovirus disease in hosts without acquired immunodeficiency syndrome and without an organ transplant. | 2001 Jan 15 |
|
Virological, clinical, and ophthalmologic features of cytomegalovirus retinitis after hematopoietic stem cell transplantation. | 2001 Jan 15 |
|
Cidofovir for cytomegalovirus infection and disease in allogeneic stem cell transplant recipients. The Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. | 2001 Jan 15 |
|
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 |
|
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 |
|
Gene therapy for hepatocellular carcinoma using two recombinant adenovirus vectors with alpha-fetoprotein promoter and Cre/lox P system. | 2001 Mar |
|
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 |
|
Top 1% of Inpatients Administered Antimicrobial Agents Comprising 50% of Expenditures: A Descriptive Study and Opportunities for Stewardship Intervention. | 2017 Mar |
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Classification Tree | Code System | Code | ||
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NDF-RT |
N0000175461
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NCI_THESAURUS |
C1556
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WHO-ATC |
J05AB14
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C29575
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NDF-RT |
N0000175459
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FDA ORPHAN DRUG |
733420
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FDA ORPHAN DRUG |
676018
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N0000175459
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LIVERTOX |
NBK548760
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NDF-RT |
N0000020060
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FDA ORPHAN DRUG |
675818
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N0000175459
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NCI_THESAURUS |
C281
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WHO-VATC |
QJ05AB14
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SUB00007MIG
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Valganciclovir
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CHEMBL1201314
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2801
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C2629
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63635
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)
SUBSTANCE RECORD