title: In vivo antiretroviral activity of stampidine in chronically feline immunodeficiency virus-infected cats.
abstract: Here we report the antiretroviral activity of the experimental nucleoside reverse transcriptase inhibitor (NRTI) compound stampidine in cats chronically infected with feline immunodeficiency virus (FIV). Notably, a single oral bolus dose of 50 or 100 mg of stampidine per kg resulted in a transient >/=1-log decrease in the FIV load of circulating peripheral blood mononuclear cells in five of six FIV-infected cats and no side effects. A 4-week stampidine treatment course with twice-daily administration of hard gelatin capsules containing 25 to 100 mg of stampidine per kg was also very well tolerated by cats at cumulative dose levels as high as 8.4 g/kg and exhibited a dose-dependent antiretroviral effect. One of three cats treated at the 25-mg/kg dose level, three of three cats treated at the 50-mg/kg dose level, and three of three cats treated at the 100-mg/kg dose level (but none of three control cats treated with placebo pills) showed a therapeutic response, as evidenced by a >/=1-log reduction in the FIV load in peripheral blood mononuclear cells within 2 weeks. The previously documented in vitro and in vivo antiretroviral activity of stampidine against primary clinical human immunodeficiency virus type 1 isolates with genotypic and/or phenotypic NRTI resistance, together with its favorable animal toxicity profile, pharmacokinetics, and in vivo antiretroviral activity in FIV-infected cats, warrants further development of this promising new NRTI compound.
authors.affiliation: Drug Discovery Program, Parker Hughes Cancer Center, St. Paul, Minnesota, USA. fatih_uckun@ih.org
authors.forename: Fatih M
authors.initials: FM
authors.lastname: Uckun
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Chen
authors.forename: Peter
authors.initials: P
authors.lastname: Samuel
authors.forename: Sharon
authors.initials: S
authors.lastname: Pendergrass
authors.forename: T K
authors.initials: TK
authors.lastname: Venkatachalam
authors.forename: Barbara
authors.initials: B
authors.lastname: Waurzyniak
authors.forename: Sanjive
authors.initials: S
authors.lastname: Qazi
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D002415:Cats; D002908:Chronic Disease; D054306:Dideoxynucleotides; D016181:Feline Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D016089:Immunodeficiency Virus, Feline / Q000187:drug effects; D018119:Stavudine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D013938:Thymidine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity
chemical_list: D019380:Anti-HIV Agents; D054306:Dideoxynucleotides; C472384:stampidine; D013938:Thymidine Monophosphate; D018119:Stavudine