Novel pharmacological strategies in the treatment of life-threatening cytomegalovirus infections. Clinical experience with continuous infusion 9-(1,3-dihydroxy-2-propoxymethyl) guanine.
Two novel antiviral pharmacologic strategies were used for therapy of life- and sight-threatening cytomegalovirus (CMV) infection; these were continuous drug infusion by portable pump and individualized patient regimen. 9-(1,3-Dihydroxy-2-propoxymethyl)-guanine (DHPG), an active and recently licensed antiviral drug against cytomegalovirus infection, was administered to five immunocompromised patients with chorioretinitis (all patients), colitis (two), and pneumonitis (three). Through dosage escalation, correlations between plasma levels, toxicity (i.e., myelosuppression), and clinical benefit were ascertained for therapy of acute disease (pneumonitis) as well as long-term therapy (chorioretinitis). Resolution of viremia, pneumonitis, colitis, and chorioretinitis was accomplished with steady-state plasma levels of DHPG approximating the mean ID50 of CMV isolates. The most notable clinical benefit was survival from CMV pneumonia and stabilization of vision. Although no adverse toxicity occurred during the DHPG continuous long-term therapy, survival was limited by the underlying disease.
Whitley
R J
RJ
Department of Pediatrics, University of Alabama, Birmingham 35294.
Connell
J
J
Markiewicz
M A
MA
Sommadossi
J P
JP
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000188:drug therapy; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003586:Cytomegalovirus Infections / Q000188:drug therapy*; D005260:Female; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007260:Infusion Pumps; D012173:Retinitis / Q000188:drug therapy / Q000382:microbiology
C040342:9-(1,3-dihydroxy-2-propoxymethyl)guanine triphosphate; D000998:Antiviral Agents; D006160:Guanosine Triphosphate