title: Toxicity and pharmacokinetics of stampidine in mice and rats.
abstract: The in vivo toxicity and pharmacokinetics of stampidine (CAS 217178-62-6), an aryl phosphate derivative of stavudine (CAS 3056-17-5) under development as a new anti-human immunodeficiency virus (anti-HIV) agent, were studied in mice and rats. Stampide was very well tolerated by both mice and rats without any toxicity at cumulative dose levels > 1 g/kg. Therapeutic micromolar plasma concentrations of stampidine and its active metabolites ala-STV-MP (CAS 180076-92-0) and STV were rapidly achieved and maintained several hours after i.p. administration of the nontoxic 25-50 mg/kg bolus doses of stampidine. The remarkable in vivo safety of stampidine warrants the further development of this promising new antiviral agent for possible clinical use in HIV-infected patients.
authors.affiliation: Drug Discovery Program, Departments of Virology, Immunology, Parker Hughes Institute, St. Paul, MN, USA. fatihuckun@ih.org
authors.forename: Fatih M
authors.initials: FM
authors.lastname: Uckun
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Chen
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Lisowski
authors.forename: Greg C
authors.initials: GC
authors.lastname: Mitcheltree
authors.forename: Taracad K
authors.initials: TK
authors.lastname: Venkatachalam
authors.forename: Douglas
authors.initials: D
authors.lastname: Erbeck
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Barbara
authors.initials: B
authors.lastname: Waurzyniak
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D054306:Dideoxynucleotides; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D051381:Rats; D011917:Rats, Inbred Lew; D018894:Reverse Transcriptase Inhibitors / Q000493:pharmacokinetics* / Q000633:toxicity*; D018119:Stavudine / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000633:toxicity*; D013938:Thymidine Monophosphate / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000633:toxicity*
chemical_list: D054306:Dideoxynucleotides; D018894:Reverse Transcriptase Inhibitors; C472384:stampidine; D013938:Thymidine Monophosphate; D018119:Stavudine