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Br J Clin Pharmacol. 1992 Mar;33(3):319-22.

Metabolism of 2',3'-dideoxyinosine (ddI) in human blood.

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Department of Pharmacology and Therapeutics, University of Liverpool.


1. 2',3'-Dideoxyinosine (ddI) has potent activity against human immunodeficiency virus (HIV). It is converted within target cells to its active form dideoxyadenosine triphosphate(ddA-TP). 2. In addition to the intracellular formation of ddA-TP, ddI can be broken down to hypoxanthine, by purine nucleoside phosphorylase (PNP) and to uric acid, by xanthine oxidase. Since PNP is present in red blood cells we have examined the metabolism of [14C]-ddI by human blood. 3. When incubated with whole blood at 37 degrees C, ddI was extensively metabolised, principally to hypoxanthine (50.4 +/- 12.5% formed at 6 h; mean +/- s.d.; n = 16). Small amounts of uric acid were formed (3.8 +/- 2.4%). 4. ddI breakdown was temperature dependent, being virtually negligible at 4 degrees C. Metabolism to hypoxanthine occurred within red blood cells. 5. The short half-life of ddI in patients is probably the result of both hepatic and erythrocytic metabolism.

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