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Antimicrobial Agents and Chemotherapy, April 2003, p. 1233-1240, Vol. 47, No. 4
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.4.1233-1240.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

In Vivo Antiretroviral Activity of Stampidine in Chronically Feline Immunodeficiency Virus-Infected Cats

Fatih M. Uckun,1,2,3,4* Chun-Lin Chen,1,5 Peter Samuel,1,6 Sharon Pendergrass,2 T. K. Venkatachalam,6 Barbara Waurzyniak,7 and Sanjive Qazi8

Drug Discovery Program,1 Clinical Immunology Program,4 Departments of Virology,2 Immunology,3 Pathology,7 Chemistry,6 Pharmaceutical Sciences,5 Bioinformatics, Parker Hughes Cancer Center, St. Paul, Minnesota8

Received 3 July 2002/ Returned for modification 20 October 2002/ Accepted 23 January 2003

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.

* Corresponding author. Mailing address: Parker Hughes Cancer Center, 2699 Patton Rd., St. Paul, MN 55113. Phone: (651) 796-5450. Fax: (651) 796-5494. E-mail: fatih_uckun{at}ih.org.

Antimicrobial Agents and Chemotherapy, April 2003, p. 1233-1240, Vol. 47, No. 4
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.4.1233-1240.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • D'Cruz, O. J., Uckun, F. M. (2005). Stampidine: a selective oculo-genital microbicide. J Antimicrob Chemother 56: 10-19 [Abstract] [Full Text]  
  • D'Cruz, O. J., Waurzyniak, B., Uckun, F. M. (2004). Antiretroviral Spermicide WHI-07 Prevents Vaginal and Rectal Transmission of Feline Immunodeficiency Virus in Domestic Cats. Antimicrob. Agents Chemother. 48: 1082-1088 [Abstract] [Full Text]  
  • D'Cruz, O. J., Samuel, P., Waurzyniak, B., Uckun, F. M. (2003). Development and Evaluation of a Thermoreversible Ovule Formulation of Stampidine, a Novel Nonspermicidal Broad-Spectrum Anti-Human Immunodeficiency Virus Microbicide. Biol. Reprod. 69: 1843-1851 [Abstract] [Full Text]  


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