title: Valacyclovir as Initial Treatment for Acute Retinal Necrosis: A Pharmacokinetic Modeling and Simulation Study.
abstract: Acute retinal necrosis (ARN) is a feared complication of infectious retinitis most commonly caused by varicella zoster virus (VZV). We performed a pharmacokinetic modeling and simulation study by integrating the existing understanding of physiology with previously published data to evaluate the vitreal penetration of oral valacyclovir for the treatment of ARN, under various dosing scenarios.
  
  
  
  We compared different oral valacyclovir dosing regimens with intravenous acyclovir. The vitreous compartment was modeled as a peripheral compartment, and paired serum and vitreal acyclovir concentrations were obtained from previously published data of adult patients with ARN undergoing vitrectomy. The efficacy threshold for vitreal acyclovir concentrations was based on the previously reported IC50values for VZV.
  
  
  
  Based on the minimum vitreal acyclovir concentrations (Cmin) relative to the mean IC50for VZV, valacyclovir 1.5 g every 8 hours performed similarly to intravenous acyclovir 700 mg every 8 hours, with the minimum concentration (Cmin) exceeding the mean IC50after the second dose. In contrast, the standard dosing regimen for herpes zoster, valacyclovir 1 g every 8 hours, performed inferiorly to the intravenous acyclovir regimen throughout the dosing interval.
  
  
  
  Modeling and simulation data support oral valacyclovir for the treatment of ARN, although the required dosing exceeds the recommended FDA dose size for herpes zoster.
authors.affiliation: a Center for Translational Medicine, School of Pharmacy , University of Maryland , Baltimore , Maryland , USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: b Department of Medicine , Drexel University College of Medicine , Philadelphia , PA , USA.
authors.forename: Aabha
authors.initials: A
authors.lastname: Jain
authors.affiliation: c Department of Opthalmology, Wills Eye Hospital , SKMC at Thomas Jefferson University , Philadelphia , PA , USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Fung
authors.affiliation: d Department of Medicine , Public Health Research Institute, New Jersey Medical School , Rutgers, Newark , NJ , USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Vinnard
authors.affiliation: a Center for Translational Medicine, School of Pharmacy , University of Maryland , Baltimore , Maryland , USA.
authors.forename: Vijay
authors.initials: V
authors.lastname: Ivaturi
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D014645:Herpesvirus 3, Human / Q000302:isolation & purification; D006801:Humans; D008962:Models, Theoretical; D015882:Retinal Necrosis Syndrome, Acute / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D012173:Retinitis / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D000077483:Valacyclovir; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000073618:Varicella Zoster Virus Infection / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D014822:Vitreous Body / Q000378:metabolism* / Q000473:pathology
chemical_list: D000998:Antiviral Agents; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir
keywords: Infection; inflammation; pharmacology; retina