Pharmacology of Ganciclovir, Valganciclovir and Aciclovir

Pharmacology

Aciclovir, Valganciclovir & GanciclovirBy Noor Aniah Azmi (MBBCh Cairo, Egypt)

Medical retina

team

presentation

Objectives

oUnderstand about each of the antiviral

oUnderstand the indications for their use

o Learn about the virus life cycle

Now, let’s learn about the

virus life cycle

Ganciclovir

Synthetic guanosine analogue

First antiviral approved for CMV treatment

How does it work?

How come it doesn’t work in some cases?

Mutations UL97 – encodes of CMV phospotransferase

.

Which virus does it attack?

In what preparations do they exist?

Zirgan ointment 0.15% - ophthalmic gel Cytovene 500 mg

What are the effects of the body on the drug?

Absorption: • Oral – very limited• t ½ : 2-6 hours

Distribution: All tissues• Especially CSF and ocular tissue

Excretion: 80-90% unchanged in urine

When do we use Ganciclovir?

1. Herpes Epithelial Keratitis Ganciclovir Gel 0.15% (Zirgan)

2. CMV Retinitis

Initial: IV 5mg/kg BD for 14-21 daysMaintenance: IV 5mg/kg OD or IV 6 mg/kg OD for 5 days/week

What are the side effects?

Bone marrow supression Neutropenia Granulocytopenia

TOXICITY Potential carcinogen Teratogen Inhibits spermatogenesis

ValganciclovirProdrug of Ganciclovir

Taken orally

Changed to Ganciclovir by intestinal/hepatic esterase

In what preparations do they exist?

Valcyte Tablet 450 mg Valcyte Oral Solution 50 mg/mL

What are the effects of the body on the drug?

Absorption: • Well-absorbed especially with fatty meals

Distribution: • Well distributed especially CSF and ocular tissues

Metabolism: • In liver & intestine changed to Ganciclovir

Excretion: 80-90% in urine

When do we use Valganciclovir?

CMV Retinitis

Initial: Oral 900 mg BD x 21 daysMaintenance: Oral 900 mg OD

AciclovirMost commonly used antiviral

Commonly used for HSV and Chickenpox

How does it work?

How come it doesn’t work in some cases?

• Deficient viral thymidine-kinase

• Mutations to viral thymidine-kinase or DNA polymerase

.

Which virus does it attack?

Herpes-simplex 1 Herpes-simplex 2 Varicella-zoster virus Epstein-Barr virus Cytomegalovirus

Most activity

In what preparations do they exist?

Zovirax ointment 3% Tablet Aciclovir 200 mg / 400 mg

What are the effects of the body on the drug?

Absorption: • Poor water-soluble• Poor oral bioavailability

Distribution: High distribution rate• T ½: 3 hours

Metabolism: Small amounts – liver

Excretion: 62-90% unchanged in urine

When do we use Aciclovir?

Herpes-Zoster Ophthalmicus Herpex Simplex Blepharitis

Herpes keratitis

What are the side effects?

Systemic Nausea, vomiting Encephalopathy IV

Local SPK Allergy