Singapore Drugs Database

Indication

For induction and maintenance in the treatment of cytomegalovirus (CMV) retinitis in immunocompromised patients, including patients with acquired immunodeficiency syndrome (AIDS). Also used in the treatment of severe cytomegalovirus (CMV) disease, including CMV pneumonia, CMV gastrointestinal disease, and disseminated CMV infections, in immunocompromised patients.

Mechanism of Action

Ganciclovir's antiviral activity inhibits virus replication. This inhibitory action is highly selective as the drug must be converted to the active form by a virus-encoded cellular enzyme, thymidine kinase (TK). TK catalyzes phosphorylation of ganciclovir to the monophosphate, which is then subsequently converted into the diphosphate by cellular guanylate kinase and into the triphosphate by a number of cellular enzymes. In vitro, ganciclovir triphosphate stops replication of herpes viral DNA. When used as a substrate for viral DNA polymerase, ganciclovir triphosphate competitively inhibits dATP leading to the formation of 'faulty' DNA. This is where ganciclovir triphosphate is incorporated into the DNA strand replacing many of the adenosine bases. This results in the prevention of DNA synthesis, as phosphodiester bridges can longer to be built, destabilizing the strand. Ganciclovir inhibits viral DNA polymerases more effectively than it does cellular polymerase, and chain elongation resumes when ganciclovir is removed.

Pharmacokinetics

Absorption

Poorly absorbed systemically following oral administration. Bioavailability under fasting conditions is approximately 5%, and when administered with food, 6 to 9% (about 30% with a fatty meal).

Distribution

* 0.74 ± 0.15 L/kg

Metabolism

Little to no metabolism, about 90% of plasma ganciclovir is eliminated unchanged in the urine.

Elimination

Clearance

* 128 +/- 63 mL/min [Patients with Renal Impairment (Clcr=50-79 mL/min)] * 57+/- 8 mL/min [Patients with Renal Impairment (Clcr=25-49 mL/min)] * 30 +/- 13 mL/min [Patients with Renal Impairment (Clcr

Toxicity

Oral, mouse LD₅₀: > 2g/kg. Intravenous, dog LD₅₀: > 150mg/kg. Symptoms of overdose include irreversible pancytopenia, worsening GI symptoms, and acute renal failure. Suspected cancer agent.

Active Ingredient/Synonyms

2-(6-Amino-purin-9-ylmethoxy)-propane-1,3-diol | 2-amino-9-((1,3-Dihydroxypropan-2-yloxy)methyl)-1H-purin-6(9H)-one | 2-amino-9-((1,3-Dihydroxypropan-2-yloxy)methyl)-3H-purin-6(9H)-one | 2-amino-9-((1,3-Dihydroxypropan-2-yloxy)methyl)-9H-purin-6-ol | 2-Amino-9-(2-hydroxy-1-hydroxymethyl-ethoxymethyl)-1,9-dihydro-purin-6-one | 2-amino-9-(2-Hydroxy-1-hydroxymethylethoxymethyl)-6,9-dihydro-1H-6-purinone | 9-((2-Hydroxy-1-(hydroxymethyl)ethoxy)methyl)guanine | 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine | GA2 | Ganciclovir | Ganciclovirum | Gancyclovir | Ganciclovir |