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.