title: Statistical analysis of Amenamevir (ASP2151) between pharmacokinetics and clinical efficacies with non-linear effect model for the treatment of genital herpes.
abstract: Amenamevir is the international non-proprietary name for ASP2151 synthesized by Astellas Pharma, Inc. It is a structurally novel class of helicase-primase inhibitor and demonstrated more potency in vitro anti-viral activity with low cytotoxicity against varicella-zoster virus (VZV), herpes simplex virus type 1 (HSV-1), and herpes simplex virus type 2 (HSV-2) than acyclovir (ACV). Phase II randomized trial assessed the safety and efficacy of ASP2151 for episodic therapy of recurrent genital herpes was conducted. Participants self-initiated with ASP2151 (100, 200, or 400 mg daily for 3 days), ASP2151 (1,200 mg as a single dose), placebo for 3 days, or Valacyclovir (500 mg twice daily for 3 days). We present a first population pharmacokinetic (PPK) modeling analysis of Amenamevir for genital herpes patients. The final model retained the effect of Weight and Albumin on CL. Statistical analysis between pharmacokinetics and clinical efficacies was done by using the time above 200 ng/mL (T200 ). T200 derived from the final PPK model to consider the correlation with Time to lesion healing and viral shedding. This finding suggested that it could be necessary to maintain the Amenamevir concentration above the threshold level to prevent the virus replication.
authors.affiliation: Astellas Pharma, Inc., Itabashi-ku, Tokyo, Japan.
authors.forename: Akitsugu
authors.initials: A
authors.lastname: Takada
authors.affiliation: Astellas Pharma, Inc., Itabashi-ku, Tokyo, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Katashima
authors.affiliation: Astellas Pharma, Inc., Itabashi-ku, Tokyo, Japan.
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kaibara
authors.affiliation: Astellas Pharma, Inc., Itabashi-ku, Tokyo, Japan.
authors.forename: Taiji
authors.initials: T
authors.lastname: Sawamoto
authors.affiliation: Astellas Pharma Global Development, Inc, Northbrook, IL, USA.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Astellas Pharma Global Development, Inc, Northbrook, IL, USA.
authors.forename: James
authors.initials: J
authors.lastname: Keirns
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006558:Herpes Genitalis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D008297:Male; D008954:Models, Biological; D017711:Nonlinear Dynamics; D010069:Oxadiazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D012008:Recurrence; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: C568714:ASP2151; D000998:Antiviral Agents; D010069:Oxadiazoles
keywords: Amenamevir; PK/PD; genital herpes; phamacokinetics; pharmacodynamics