      Document 0208
 DOCN  DRG0208
 UNIQUE IDENTIFIER        DRG-0039
 NAME OF SUBSTANCE        Dideoxyadenosine [Merck Index 1989]
 REGISTRY NUMBER          4097-22-7
 STANDARD CHEMICAL NAME   2',3' Dideoxyadenosine [USP DI 1995]
 SYNONYMS                 ddA [CHEMLINE]
 SYNONYMS                 Adenosine, 2',3'-dideoxy- [CHEMLINE]
 SYNONYMS                 ddAdo [Merck Index 1989]
 SYNONYMS                 6-Amino-9-(2',3'-dideosy-beta-D-glycero-pento-
                          furanosyl) purine [Merck Index 1989]
 SYNONYMS                 DDA [Merck Index 1989]
 PROTOCOL ID NUMBERS      NCI 87 C-158D
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: 2',3-Dideoxyadenosine (ddA),
                          the pro-drug for 2',3'-Dideoxyinosine (ddI),
                          is deaminated by serum adenosine deaminases
                          to ddI. ddA possesses antiviral activity with
                          less toxicity than Zidovudine
                          (Azidothymidine; AZT). ddI is a precursor to
                          dideoxyadenosinetriphosphate, which is
                          believed to exert antiviral activity by
                          serving as a substrate and inhibitor for HIV
                          reverse transcriptase. ddI blocks HIV
                          replication by blocking HIV infection of
                          macrophages. Since ddA is rapidly deaminated
                          to ddI by adenosine deaminase, only ddI is
                          detected in plasma of patients receiving ddA.
                          Doses of ddI from 0.2 to 1.6 mg/kg produce
                          peak plasma levels of 0.6 to 5 mu M
                          respectively, within the range of
                          effectiveness seen in vitro (ED50 2-5 muM vs.
                          HIV in the ATH8 test system). ddI has a
                          plasma half life of approximately 35 minutes.
                          This may not be representative of the
                          biological effect of the compound, however,
                          as both ddA and ddI are converted
                          intracellularly to the active species ddATP
                          which has an intracellular half-life of up to
                          24 hours. In humans, ddI is detectable in
                          cerebral spinal fluid (CSF). [AmFAR Tx Dir
                          1988 December] [Int Conf AIDS. 1989 Jun 4-9;5
                          (abstract no WBP 275)]
 DISEASES STUDIED/TREATED Primary HIV infection [USP DI 1995]
 CLASSIFICATION CODE      Antiretroviral [Drug Evaluations Annual 1995]
 SUBSTANCE INTERACTIONS   ddI, which is formed from ddA, should not be
                          used with adenine deaminase inhibitors, such
                          as Deoxycoformycin. [NIAID ACTG 064]
 ADVERSE EFFECTS          Severe nephrotoxicity was noted from oral
                          dosing of animals with non-formulated ddA,
                          but not with non-formulated ddI nor with
                          intraperitoneal or intravenous administration
                          of either ddA or ddI. [AmFAR Tx Dir Dec 1988]
                          In vitro, ddI is 10 times less toxic than
                          either Azidothymidine or
                          2',3'-Dideoxycytidine, but may cause mild
                          headaches and light-headedness. [NIAID ACTG
                          064] [AmFAR Tx Dir Dec 1988]
 CONTRAINDICATIONS        ddI, which is formed from ddA, should not be
                          used by pregnant or lactating women or by
                          patients with a history of seizure disorders
                          or heart disease. [NIAID ACTG 064]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Purine nucleoside
                          derivative; adenosine minus two oxygen atoms
                          at the 2 and 3 positions of the ribofuranosyl
                          ring. Structurally analogous to
                          2',3'-Dideoxyinosine, its deamination product
                          [AmFAR Tx Dir Dec 1988]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C10H13N5O2 [Merck Index
                          1989]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 235.25 [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Crystalline powder
                          [AmFAR Tx Dir Dec 1988]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 184-186 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C51.06%, H5.57%,
                          N29.77%, O13.60% [Merck Index 1989]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Structurally analogous to ddI,
                          which is used as a sterile solution in vials
                          [NIAID ACTG 064]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Structurally analogous to
                          ddI, which is administered via IV infusion
                          [NIAID ACTG 064]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: (Note: Ingestion of an
                          antacid is required prior to oral
                          adminitration of ddI since ddI is acid
                          unstable). [NIAID ACTG 064]
 SUBSTANCE DELIVERY DATA  STORAGE: Structurally analogous to ddI, which
                          is stored at 2-30 C. [NIAID ACTG 064]
 REFERENCES               Morse GD, Shelton MJ, O'Donnell AM.
                          Comparative pharmacokinetics of antiviral
                          nuceoside analogues. Clin Pharmacokinet. 1993
                          Feb;24(2):101-23.
 REFERENCES               Luster MI, Rosenthal GJ, Cao W, Thompson MB,
                          Munson AE, Prejean JD, Shopp G, Fuchs BA,
                          Germolec DR, Tomaszewski JE. Experimental
                          studies of the hematologic and immune system
                          toxicity of nucleoside derivatives used
                          against HIV infection. Int J Immunopharmacol.
                          1991;13 Suppl 1:99-107.
 REFERENCES               Hartman NR, Yarchoan R, Pluda JM, Thomas RV,
                          Marczyk KS, Broder S, Johns DG.
                          Pharmacokinetics of 2',3'-dideoxyadenosine
                          and 2',3'-dideoxyinosine in patients with
                          severe human immunodeficiency virus
                          infection. Clin Pharmacol Ther. 1990
                          May;47(5):647-54.
 REFERENCES               Yarchoan R, Broder S. PHARMACOLOGIC TREATMENT
                          OF HIV INFECTION. AIDS: Etiology, Diagnosis,
                          Treatment, and Prevention. Second Edition.
                          DeVit VT Jr et al, ed. Philadephia,
                          Lippincott, p. 277-93, 1988.
 ENTRY MONTH              8906
 LAST REVISION DATE       960310
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
