Pharmacokinetics and safety of FV-100, a novel oral anti-herpes zoster nucleoside analogue, administered in single and multiple doses to healthy young adult and elderly adult volunteers

Antimicrob Agents Chemother. 2011 Jun;55(6):2847-54. doi: 10.1128/AAC.01446-10. Epub 2011 Mar 28.

Abstract

FV-100 is the prodrug of the highly potent anti-varicella zoster virus bicyclic nucleoside analogue CF-1743. To characterize the pharmacokinetics and safety of oral FV-100, 3 randomized, double-blind, placebo-controlled clinical trials were conducted: (i) a single-ascending-dose study in 32 healthy subjects aged 18 to 55 years (100-, 200-, 400-, and 800-mg doses) with an evaluation of the food effect in the 400-mg group; (ii) a multiple-ascending-dose study in 48 subjects aged 18 to 55 years (100 mg once daily [QD], 200 mg QD, 400 mg QD, 400 mg twice a day, and 800 mg QD for 7 days); and (iii) a 2-part study in subjects aged 65 years and older with a single 400-mg dose in 15 subjects and a 400-mg QD dosing regimen for 7 days in 12 subjects. FV-100 was rapidly and extensively converted to CF-1743, the concentration of which remained above that required to reduce viral activity by 50% for the 24-hour dosing period. Renal excretion of CF-1743 was very low. A high-fat meal reduced exposure to CF-1743; a low-fat meal did not. Pharmacokinetic parameters for the elderly subjects were comparable to those for the younger subjects. FV-100 was well tolerated by all subjects. The pharmacokinetic and safety profiles of FV-100 support its continued investigation for the treatment of herpes zoster and prevention of postherpetic neuralgia with once-daily dosing and without dose modifications for elderly or renally impaired patients.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Antiviral Agents / pharmacokinetics*
  • Double-Blind Method
  • Female
  • Herpes Zoster / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Prodrugs / pharmacokinetics*
  • Pyrimidine Nucleosides / administration & dosage
  • Pyrimidine Nucleosides / adverse effects
  • Pyrimidine Nucleosides / blood
  • Pyrimidine Nucleosides / pharmacokinetics*

Substances

  • Antiviral Agents
  • Cf 1743
  • FV-100
  • Prodrugs
  • Pyrimidine Nucleosides