Ganciclovir

2 - [( 2-amino -6-hydroxy -purin- 9 -yl) methoxy] - propan-1 ,3-diol

• J05AB06
• S01AD09

Virostatikum

Risk

• > 2000 mg · kg -1 ( LD50, mouse, oral)
• 900 mg · kg -1 ( LD50, mouse, i.v.)

Template: Infobox chemical / molecular formula search available

Ganciclovir is an analogue of the nucleobase guanine. It is used as an antiviral agent against herpes viruses.

Chemistry

Ganciclovir is structurally related to acyclovir and penciclovir.

Application

Ganciclovir is mainly used in diseases caused by cytomegalovirus ( CMV, human herpes virus synonymously 5 / HHV 5) are caused. Of particular importance are CMV infections

• Immune deficiency in the context of transplants or AIDS, as well as
• During pregnancy.

(For details see main article cytomegalovirus ).

Ganciclovir is also effective in herpetic keratitis ( " ocular herpes " ) and can be administered topically here in the form of eye gel.

Experimentally, it is also used for gene therapy of malignant degeneration.

Operation

Although ganciclovir is effective against all human infested herpes viruses, but mainly against cytomegalovirus ( CMV ) ( is about 10 -fold more phosphorylated in CMV - infected cells and thus activated in normal cells ). In infected cells, it is by viral kinases first to monophosphate, then phosphorylated by cellular kinases to the 5'- triphosphate. Particularly in virus infected cells, it is first converted by the cellular Guaninkinase in ganciclovir triphosphate to be installed as a synthetic nucleoside analogue into viral DNA, thereby resulting in chain termination by the viral polymerase is a base after installation of the ganciclovir terminates chain elongation.

Administration and pharmacokinetics

Since its oral bioavailability is less than 5 %, it is usually given in two doses of 5 mg per kg body weight in twelve hours apart as an infusion. With a pH of 11, the solution is strongly alkaline, so that the infusion must be given slowly via a large vein. For the same reason incorrect infusions should be avoided ( in an artery, the subcutaneous tissue or muscles ).

In patients an infusion time of 60 minutes of mean plasma concentrations of about 6 mg / l were obtained. The substance is primarily excreted unchanged by the kidney, with elimination half -life is with normal renal function is about 1.5 to 3 hours. Dose adjustment in patients with impaired creatinine clearance must be done.

As oral Verarbreichung 1 g three times is taken daily with meals; topical applications in gel form around the eyes are on the German market since 2006.

Adverse effects

Since ganciclovir significantly higher toxic properties as, for example, acyclovir has ( it is in non- infected cells significantly more phosphorylated than acyclovir = enabled ), can be expected high rates of side effects:

The most commonly observed side effects are neutropenia, thrombocytopenia and anemia, less frequently occur: eosinophilia, elevation of transaminases or urea and creatinine concentrations in plasma; central nervous system side effects such as dizziness, headache, hallucinations, convulsions; Symptoms of the gastrointestinal tract (nausea, vomiting and diarrhea); Skin manifestations.

Trade names

Cymeven (D), Cymevene (A, CH), Virgan (D)