Effect of Liver Disease on Pharmacokinetics and Toxicity of 9- -D-Arabinofuranosyladenine-5'-Phosphate

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Abstract
Plasma levels of 9-β-D-arabinofuranosyladenine-5′-phosphate (ara-AMP) and its metabolites 9-β-D-arabinofuranosyladenine (ara-A) and 9-β-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 3D-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.

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