Benzylacyclouridine reverses azidothymidine-induced marrow suppression without impairment of anti-human immunodeficiency virus activity.

Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.

Benzylacyclouridine reverses azidothymidine-induced marrow suppression without impairment of anti-human immunodeficiency virus activity.

Blood. 1990 Dec 1;76(11):2210-5. Unique Identifier : AIDSLINE MED/91077425
Calabresi P; Falcone A; St Clair MH; Wiemann MC; Chu SH; Darnowski JW; Department of Medicine, Roger Williams General Hospital,; Providence, RI 02908.

Abstract: Increased extracellular concentrations of uridine (Urd) have been reported to reduce, in vitro, azidothymidine (AZT)-induced inhibition of human granulocyte-macrophage progenitor cells without impairment of its antihuman immunodeficiency virus (HIV) activity. Because of the clinical toxicities associated with chronic Urd administration, the ability of benzylacyclouridine (BAU) to effect, in vivo, AZT-induced anemia and leukopenia was assessed. This agent inhibits Urd catabolism and, in vivo, increases the plasma concentration of Urd in a dose-dependent manner, without Urd-related toxicity. In mice rendered anemic and leukopenic by the administration of AZT for 28 days in drinking water (1.5 mg/mL), the continued administration of AZT plus daily BAU (300 mg/kg, orally) partially reversed AZT-induced anemia and leukopenia (P less than .05), increased peripheral reticulocytes (to 4.9%, P less than .01), increased cellularity in the marrow, and improved megaloblastosis. When coadministered with AZT from the onset of drug administration, BAU reduced AZT-induced marrow toxicity. In vitro, at a concentration of 100 mumol/L, BAU possesses minimal anti-HIV activity and has no effect on the ability of AZT to reverse the HIV-induced cytopathic effect in MT4 cells. The clinical and biochemical implications of these findings are discussed.

Keywords: Anemia/*CHEMICALLY INDUCED/*PREVENTION & CONTROL Animal Cell Line Cytopathogenic Effect, Viral/DRUG EFFECTS Female HIV/*DRUG EFFECTS Leukopenia/CHEMICALLY INDUCED/*PREVENTION & CONTROL Mice Mice, Inbred BALB C Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Uracil/*ANALOGS & DERIVATIVES/ADMINISTRATION & DOSAGE/THERAPEUTIC USE Uridine/BLOOD Zidovudine/PHARMACOLOGY/*TOXICITY JOURNAL ARTICLE
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M9140661

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