Effect of liver disease on pharmacokinetics and toxicity of 9-beta-D-arabinofuranosyladenine-5-phosphate.
Plasma levels of 9-beta-D-arabinofuranosyladenine-5'-phosphate (ara-AMP) and its metabolites 9-beta-D-arabinofuranosyladenine (ara-A  and 9-beta-D-arabinofuranosylhypoxanthine (ara-Hx) were determined by high-performance liquid chromatography in four patients with chronic active hepatitis positive for hepatitis B surface antigen and eight patients with severe herpesvirus infections and normal liver function. Ara-AMP was given intravenously over a 30-min period in doses ranging from 10 to 30 mg of ara-A equivalent/kg per day. The metabolism of ara-AMP did not differ significantly between the two patient groups. Ara-AMP was quickly converted to ara-A, which was rapidly deaminated to ara-Hx. The mean half-lives of ara-AMP, ara-A, and ara-Hx were 0.14 hr, 0.17 hr, and 3.5 hr, respectively. Thus, ara-AMP is rapidly metabolized and does not act as a depot form of ara-A. Patients with chronic active hepatitis demonstrated increased bone marrow sensitivity to ara-AMP and a musculoskeletal pain syndrome not observed in patients treated for herpesvirus infections.
D000328:Adult; D000368:Aged; D001087:Arabinonucleosides / Q000097:blood; D001088:Arabinonucleotides / Q000097:blood*; D002648:Child; D005260:Female; D006509:Hepatitis B / Q000378:metabolism*; D006566:Herpesviridae Infections / Q000188:drug therapy; D006801:Humans; D007042:Hypoxanthines / Q000097:blood; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D014740:Vidarabine / Q000097:blood; D001084:Vidarabine Phosphate / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use
D001087:Arabinonucleosides; D001088:Arabinonucleotides; D007042:Hypoxanthines; D001084:Vidarabine Phosphate; C008099:hypoxanthine arabinoside; D014740:Vidarabine