Toxicity and pharmacokinetics of stampidine in mice and rats.
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.
Uckun
Fatih M
FM
Drug Discovery Program, Departments of Virology, Immunology, Parker Hughes Institute, St. Paul, MN, USA. fatihuckun@ih.org
Chen
Chun-Lin
CL
Lisowski
Elizabeth
E
Mitcheltree
Greg C
GC
Venkatachalam
Taracad K
TK
Erbeck
Douglas
D
Chen
Hao
H
Waurzyniak
Barbara
B
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*
D054306:Dideoxynucleotides; D018894:Reverse Transcriptase Inhibitors; C472384:stampidine; D013938:Thymidine Monophosphate; D018119:Stavudine