title: 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.
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.
authors: SAJE Consulting LLC, 1101 East 33rd Street, Suite C310, Baltimore, Maryland 21218, USA.
authors: Helen S
authors: HS
authors: Pentikis
authors: Mark
authors: M
authors: Matson
authors: George
authors: G
authors: Atiee
authors: Brian
authors: B
authors: Boehlecke
authors: Jeff T
authors: JT
authors: Hutchins
authors: Joseph M
authors: JM
authors: Patti
authors: Geoffrey W
authors: GW
authors: Henson
authors: Amy
authors: A
authors: Morris
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000998:Antiviral Agents / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D005260:Female; D006562:Herpes Zoster / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011355:Prodrugs / Q000493:pharmacokinetics*; D011741:Pyrimidine Nucleosides / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000998:Antiviral Agents; C500967:Cf 1743; C526677:FV-100; D011355:Prodrugs; D011741:Pyrimidine Nucleosides