{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T21:16:58Z","timestamp":1773695818397,"version":"3.50.1"},"reference-count":38,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2013,3,1]],"date-time":"2013-03-01T00:00:00Z","timestamp":1362096000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            ASP2151 (amenamevir) is a helicase-primase inhibitor against herpes simplex virus 1 (HSV-1), HSV-2, and varicella zoster virus. Here, to determine and analyze the correlation between the pharmacodynamic (PD) and pharmacokinetic (PK) parameters of ASP2151, we examined the PD profile of ASP2151 using\n            <jats:italic>in vitro<\/jats:italic>\n            plaque reduction assay and a murine model of HSV-1 infection. ASP2151 inhibited the\n            <jats:italic>in vitro<\/jats:italic>\n            replication of HSV-1 with a mean 50% effective concentration (EC\n            <jats:sub>50<\/jats:sub>\n            ) of 14 ng\/ml. In the cutaneously HSV-1-infected mouse model, ASP2151 dose dependently suppressed intradermal HSV-1 growth, with the effect reaching a plateau at a dose of 30 mg\/kg of body weight\/day. The dose fractionation study showed that intradermal HSV-1 titers were below the detection limit in mice treated with ASP2151 at 100 mg\/kg\/day divided into two daily doses and at 30 or 100 mg\/kg\/day divided into three daily doses. The intradermal HSV-1 titer correlated with the maximum concentration of drug in serum (\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            ), the area under the concentration-time curve over 24 h (AUC\n            <jats:sub>24h<\/jats:sub>\n            ), and the time during which the concentration of ASP2151 in plasma was above 100 ng\/ml (\n            <jats:italic>T<\/jats:italic>\n            <jats:sub>&gt;100<\/jats:sub>\n            ). The continuous infusion of ASP2151 effectively decreased intradermal HSV-1 titers below the limit of detection in mice in which the ASP2151 concentration in plasma reached 79 to 145 ng\/ml. Our findings suggest that the antiviral efficacy of ASP2151 is most closely associated with the PK parameter\n            <jats:italic>T<\/jats:italic>\n            <jats:sub>&gt;100<\/jats:sub>\n            in HSV-1-infected mice. Based on these results, we propose that a plasma ASP2151 concentration exceeding 100 ng\/ml for 21 to 24 h per day provides the maximum efficacy in HSV-1-infected mice.\n          <\/jats:p>","DOI":"10.1128\/aac.01803-12","type":"journal-article","created":{"date-parts":[[2012,12,29]],"date-time":"2012-12-29T07:14:08Z","timestamp":1356765248000},"page":"1339-1346","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":25,"title":["Pharmacokinetics and Pharmacodynamics of ASP2151, a Helicase-Primase Inhibitor, in a Murine Model of Herpes Simplex Virus Infection"],"prefix":"10.1128","volume":"57","author":[{"given":"Kiyomitsu","family":"Katsumata","sequence":"first","affiliation":[{"name":"Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Ibaraki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Chono","sequence":"additional","affiliation":[{"name":"Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Ibaraki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kota","family":"Kato","sequence":"additional","affiliation":[{"name":"Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Ibaraki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiaki","family":"Ohtsu","sequence":"additional","affiliation":[{"name":"Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Ibaraki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shoji","family":"Takakura","sequence":"additional","affiliation":[{"name":"Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Ibaraki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toru","family":"Kontani","sequence":"additional","affiliation":[{"name":"Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Ibaraki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Ibaraki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","first-page":"2479","volume-title":"Fields virology","author":"Pellet PE","year":"2007","unstructured":"PelletPE RoizmanB. 2007. The family Herpesviridae: a brief introduction, p 2479\u20132499. In KnipeDM HowleyPM GriffinDE LambRA MartinMA RoizmanB StrausSE (ed), Fields virology, 5th ed, vol 2. Lippincott Williams & Wilkins, Philadelphia, PA.","edition":"5"},{"key":"e_1_3_3_3_2","first-page":"2501","volume-title":"Fields virology","author":"Roizman B","year":"2007","unstructured":"RoizmanB KnipeD WhitleyR. 2007. Herpes simplex viruses, p 2501\u20132601. In KnipeDM HowleyPM GriffinDE LambRA MartinMA RoizmanB StrausSE (ed), Fields virology, 5th ed, vol 2. Lippincott Williams & Wilkins, Philadelphia, PA.","edition":"5"},{"key":"e_1_3_3_4_2","first-page":"45","article-title":"Prevention strategies: herpes zoster, post-herpetic neuralgia and immunogenicity","volume":"14","author":"Levin MJ","year":"2007","unstructured":"LevinMJ SchmaderK. 2007. Prevention strategies: herpes zoster, post-herpetic neuralgia and immunogenicity. 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