Drug Groups

approved; investigational

Description

Valaciclovir (INN) or valacyclovir (USAN) is an antiviral drug used in the management of herpes simplex and herpes zoster (shingles). It is a prodrug, being converted in vivo to aciclovir. It is marketed by GlaxoSmithKline under the trade name Valtrex or Zelitrex. [Wikipedia]

Indication

For the treatment or suppression of cold sores (herpes labialis), herpes zoster (shingles), genital herpes in immunocompetent individuals, and recurrent genital herpes in HIV-infected individuals.

Pharmacology

Valaciclovir (INN) or Valacyclovir (USAN) is a prodrug and synthetic purine nucleoside analogue with inhibitory activity against herpes simplex virus types 1 (HSV-1), 2 (HSV-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV). Valaciclovir is almost completely converted to acyclovir and L-valine. The inhibitory activity of valaciclovir is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts acyclovir into acyclovir monophosphate, which is then converted into acyclovir diphosphate and triphosphate by cellular enzymes. Acyclovir is selectively converted to the active triphosphate form by cells infected with herpes viruses.

Toxicity

Adverse effects of overexposure might include headache and nausea.

Affected Organisms

Biotransformation

Valaciclovir is rapidly and almost entirely (~99%) converted to the active compound, acyclovir, and L-valine by first-pass intestinal and hepatic metabolism by enzymatic hydrolysis. Neither valaciclovir nor acyclovir is metabolized by cytochrome P450 enzymes.

Absorption

After oral administration, valaciclovir hydrochloride is rapidly absorbed from the gastrointestinal tract. The absolute bioavailability of acyclovir after administration of valaciclovir is 54.5% ± 9.1%.

Half Life

2.5-3.3 hours

Protein Binding

13-18%

Elimination

Acyclovir accounted for 89% of the radioactivity excreted in the urine.

Clearance

* Renal cl=255 +/- ?86 mL/min [healthy]
* apparent cl=86.3 +/- 21.3 mL/min/1.73?m2 [dialysis patients]
* apparent cl=679.16 +/- 162.76 mL/min/1.73?m2 [healthy]

References

External Links