Azidothymidine (AZT) is the only approved drug for treatment of acquired immunodeficiency syndrome caused by human immunodeficiency virus. The drug is known to be metabolized by mammalian systems. The objectives of this study were: 1) to investigate the biologic fate of AZT using whole-body autoradiography; and 2) to compare the biologic fate of AZT with that of the parent molecule thymidine (dThd). Male Sprague-Dawley mice were given (intravenously) a tracer dose of [2-14C]AZT (273 μCi/kg) or [2-14C]dThd (218 μCi/kg). Treated animals were sacrificed at various time periods (2 min, 5 min, 4 hr and 24 hr) and processed for whole-body autoradiography. Tissue distribution of radioactivity in the autoradiographs was quantitated using computer-aided image analysis. The elimination of AZT and dThd was also examined by radiochemical analyses of urine, feces and expired air of treated animals over a 24-hr period. Twentyfour hr following AZT treatment, the radioactivity excreted in urine, feces and in exhaled air (as 14CO2) accounted for 86, 4.6 and 3.7% of the dose, respectively. Within 2 min after administration of AZT, maximum radioactivity was detected in the kidney. The brain, spinal cord and testes were conspicuous because of virtual lack of radioactivity. All other parenchymatous organs (liver, lung, heart and spleen) had apparent similar levels of radioactivity that were higher than those in the connective tissues. At a later time period (4 hr), the radioactivity in most organs was eliminated except in the renal medulla, contents of gastrointestinal tract, urinary bladder and mouth cavity. Contrary to [2-14C]dThd, 24 hr after administration, a minimal amount of radioactivity was detected in [2-14C]AZT-treated animals. In conclusion, our study suggests that: 1) AZT distribution and elimination patterns are distinctively different from that of dThd; 2) AZT is homogeneously distributed to all parenchymatous organs; 3) AZT is predominantly excreted unmetabolized by the kidney; and 4) AZT does not cross the blood-brain and blood-testes barriers.
|Original language||English (US)|
|Number of pages||8|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - 1991|
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