title: Valacyclovir pharmacokinetics and exploratory pharmacodynamics in young adults with Epstein-Barr virus infectious mononucleosis.
abstract: Primary Epstein-Barr virus (EBV) infection often results in infectious mononucleosis and is associated with serious sequelae. No treatment is approved for EBV infection, and an antiviral intervention would be significant. The objectives of this study are to characterize the pharmacokinetics and explore the pharmacodynamics of acyclovir in plasma and oral washings of 8 subjects receiving 7 days of valacyclovir 1500 mg twice daily for EBV infectious mononucleosis. Virologic and clinical responses are assessed over 12 days. Acyclovir is measured by liquid chromatography/ultraviolet detection. EBV DNA is quantitated by TaqMan polymerase chain reaction. NONMEM VI and linear regression are used for data analysis. Acyclovir profiles in plasma and oral washings are consistent with a 1-compartment model. Final model estimates of clearance, volume of distribution, and fraction of acyclovir in oral wash supernatant are 49.9 L/h, 74.1 L, and 1.14%, respectively. The quantity of EBV DNA in oral washings and blood, and the severity of illness, measured by a graded scale, decrease during treatment. After treatment, viral rebound occurs in oral washings but not in blood, and the severity of illness continues to decline. Acyclovir pharmacokinetic parameters do not correlate with response metrics. These results support further studies of valacyclovir for EBV infectious mononucleosis.
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, 420 Delaware St. SE, Minneapolis, MN 55455, USA. wynnx004@umn.edu
authors.forename: Heather E
authors.initials: HE
authors.lastname: Vezina
authors.forename: Henry H
authors.initials: HH
authors.lastname: Balfour
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Weller
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Anderson
authors.forename: Richard C
authors.initials: RC
authors.lastname: Brundage
mesh_terms: D000208:Acute Disease; D000212:Acyclovir / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000293:Adolescent; D000998:Antiviral Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D004279:DNA, Viral / Q000032:analysis / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D004854:Herpesvirus 4, Human; D006801:Humans; D007244:Infectious Mononucleosis / Q000188:drug therapy*; D016014:Linear Models; D008297:Male; D015233:Models, Statistical; D009055:Mouth / Q000378:metabolism / Q000821:virology; D011446:Prospective Studies; D000077483:Valacyclovir; D014633:Valine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir