Ganciclovir

From Wikipedia, the free encyclopedia - View original article

Ganciclovir
Ganciclovir structure.svg
Ganciclovir ball-and-stick.png
Systematic (IUPAC) name
2-amino-9-{[(1,3-dihydroxypropan-2-yl)oxy]methyl}-6,9-dihydro-3H-purin-6-one
Clinical data
Trade namesCytovene
AHFS/Drugs.commonograph
MedlinePlusa605011
Pregnancy cat.
Legal status
RoutesIV, oral, intravitreal
Pharmacokinetic data
Bioavailability5% (oral)
Metabolismguanylate kinase (CMV UL97 gene product)
Half-life2.5–5 hours
ExcretionRenal
Identifiers
CAS number82410-32-0 YesY
ATC codeJ05AB06 S01AD09
PubChemCID 3454
DrugBankDB01004
ChemSpider3336 YesY
UNIIP9G3CKZ4P5 YesY
KEGGD00333 YesY
ChEBICHEBI:465284 YesY
ChEMBLCHEMBL182 YesY
Chemical data
FormulaC9H13N5O4 
Mol. mass255.23 g/mol
 YesY (what is this?)  (verify)
 
Jump to: navigation, search
Ganciclovir
Ganciclovir structure.svg
Ganciclovir ball-and-stick.png
Systematic (IUPAC) name
2-amino-9-{[(1,3-dihydroxypropan-2-yl)oxy]methyl}-6,9-dihydro-3H-purin-6-one
Clinical data
Trade namesCytovene
AHFS/Drugs.commonograph
MedlinePlusa605011
Pregnancy cat.
Legal status
RoutesIV, oral, intravitreal
Pharmacokinetic data
Bioavailability5% (oral)
Metabolismguanylate kinase (CMV UL97 gene product)
Half-life2.5–5 hours
ExcretionRenal
Identifiers
CAS number82410-32-0 YesY
ATC codeJ05AB06 S01AD09
PubChemCID 3454
DrugBankDB01004
ChemSpider3336 YesY
UNIIP9G3CKZ4P5 YesY
KEGGD00333 YesY
ChEBICHEBI:465284 YesY
ChEMBLCHEMBL182 YesY
Chemical data
FormulaC9H13N5O4 
Mol. mass255.23 g/mol
 YesY (what is this?)  (verify)

Ganciclovir INN /ɡænˈskləvɪər/ or DHPG (9-(1,3-dihydroxy-2-propoxymethyl)guanine, alternative spelling: "Gancyclovir") is an antiviral medication used to treat cytomegalovirus (CMV) infections. Ganciclovir sodium is marketed under the trade names Cytovene and Cymevene (Roche). Ganciclovir for ocular use is marketed under the trade name Vitrasert (Bausch & Lomb). A prodrug form with improved oral bioavailability (valganciclovir) has also been developed.

Mechanism of action[edit]

Ganciclovir is a synthetic analogue of 2′-deoxy-guanosine. It is first phosphorylated to ganciclovir monophosphate by a viral kinase encoded by the cytomegalovirus (CMV) gene UL97 during infection. Subsequently, cellular kinases catalyze the formation of ganciclovir diphosphate and ganciclovir triphosphate, which is present in 10-fold greater concentrations in CMV or herpes simplex virus (HSV)-infected cells than uninfected cells.

Ganciclovir triphosphate is a competitive inhibitor of deoxyguanosine triphosphate (dGTP) incorporation into DNA and preferentially inhibits viral DNA polymerases more than cellular DNA polymerases. In addition, ganciclovir triphosphate serves as a poor substrate for chain elongation, thereby disrupting viral DNA synthesis by a second route.

Clinical use[edit]

Indications[edit]

Ganciclovir is indicated for:[1]

It is also used for acute CMV colitis in HIV/AIDS and CMV pneumonitis in immunosuppressed patients.

Ganciclovir has also been used with some success in treating Human herpesvirus 6 infections.[2]

Ganciclovir has also been found to be an effective treatment for herpes simplex virus epithelial keratitis.[3]

Adverse effects[edit]

Ganciclovir is commonly associated with a range of serious haematological adverse effects. Common adverse drug reactions (≥1% of patients) include: granulocytopenia, neutropenia, anaemia, thrombocytopenia, fever, nausea, vomiting, dyspepsia, diarrhea, abdominal pain, flatulence, anorexia, raised liver enzymes, headache, confusion, hallucination, seizures, pain and phlebitis at injection site (due to high pH), sweating, rash, itch, increased serum creatinine and blood urea concentrations.[1]

Toxicity[edit]

Ganciclovir is considered a potential human carcinogen, teratogen, and mutagen. It is also considered likely to cause inhibition of spermatogenesis. Thus, it is used judiciously and handled as a cytotoxic drug in the clinical setting.[1][4]

Pharmacokinetics[edit]

Absorption of the oral form is very limited—about 5% fasting, about 8% with food. It achieves a concentration in the central nervous system of about 50% of the plasma level. About 90% of plasma ganciclovir is eliminated unchanged in the urine, with a half-life of 2–6 hours, depending on renal function (elimination takes over 24 hours in end-stage renal disease).

Administration[edit]

Acute infections are treated in two phases:

Stable disease is treated with 1000 mg orally three times daily. Similar dosing is used to prevent disease in high-risk patients, such as those infected with human immunodeficiency virus (HIV) or those with organ transplants.

Ganciclovir is also available in slow-release formulations for insertion into the vitreous humour of the eye, as treatment for CMV retinitis (associated with HIV infection).

A topical ophthalmic gel preparation of ganciclovir was recently approved for the treatment of acute herpes simplex keratitis.

References[edit]

  1. ^ a b c Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3
  2. ^ Nakano (2009). "Detection and identification of U69 gene mutations encoded by ganciclovir-resistant human herpesvirus 6 using denaturing high-performance liquid chromatography". 
  3. ^ Wilhelmus KR (2010). "Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis". Cochrane Database Syst Rev 12: CD002898. doi:10.1002/14651858.CD002898.pub4. PMID 21154352. 
  4. ^ Roche Products Pty Ltd. Cymevene (Australian Approved Product Information). Dee Why (NSW): Roche; 2005.

Further reading[edit]